bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of numerical methods for computing the repeated Compton scattering of photons in isotropic media
Authors: Acharya Sandeep Kumar , Chluba Jens , Sarkar Abir 
Published: August 2021

ABSTRACT
Repeated Compton scattering of photons with thermal electrons is one of the fundamental processes at work in many astrophysical plasma. Solving the exact evolution equations is hard and one common simplification is based on Fokker–Planck (FP) approximations of the Compton collision term. Here we carry out a detailed numerical comparison of several FP approaches with the exact scattering kernel solution for a range of test problems assuming isotropic media and thermal electrons at various temperatures. The Kompaneets equation, being one of the most widely used FP approximations, fails to account for Klein–Nishina corrections and enhanced Doppler boosts and recoil at high energies. These can be accounted for with an alternative FP approach based on the exact first and second moments of the scattering kernel. As demonstrated here, the latter approach works very well in dilute media, but inherently fails to reproduce the correct equilibrium solution in the limit of many scattering. Conditions for the applicability of the FP approximations are clarified, overall showing that the Kompaneets equation provides the most robust approximation to the full problem, even if inaccurate in many cases. We close our numerical analysis by briefly illustrating the solutions for the spectral distortions of the cosmic microwave background (CMB) after photon injection at redshift z ≲ 105, when double Compton and Bremsstrahlung emission can be omitted. We demonstrate that the exact treatment using the scattering kernel computed with cspack is often needed. This work should provide an important step towards accurate computations of the CMB spectral distortions from high-energy particle cascades.
Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice
Authors: Chuntova Pavlina , Hou Yafei , Naka Ryosuke , Yamamichi Akane , Chen Tiffany , Goretsky Yitzhar , Hatae Ryusuke , Nejo Takahide , Kohanbash Gary , Mende Abigail L , Montoya Megan , Downey Kira M , Diebold David , Skinner Jayne , Liang Hong-Erh , Schwer Bjoern , Okada Hideho 
Published: August 2021

Abstract

Background
Rigorous preclinical studies of chimeric antigen receptor (CAR) immunotherapy will require large quantities of consistent and high-quality CAR-transduced T (CART) cells that can be used in syngeneic mouse glioblastoma (GBM) models. To this end, we developed a novel transgenic (Tg) mouse strain with a fully murinized CAR targeting epidermal growth factor receptor variant III (EGFRvIII).

Methods
We first established the murinized version of EGFRvIII-CAR and validated its function using a retroviral vector (RV) in C57BL/6J mice bearing syngeneic SB28 GBM expressing EGFRvIII. Next, we created C57BL/6J-background Tg mice carrying the anti-EGFRvIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. We bred these mice with CD4-Cre Tg mice to allow CAR expression on T cells and evaluated the function of the CART cells both in vitro and in vivo. To inhibit immunosuppressive myeloid cells within SB28 GBM, we also evaluated a combination approach of CART and an anti-EP4 compound (ONO-AE3-208).

Results
Both RV- and Tg-CART cells demonstrated specific cytotoxic activities against SB28-EGFRvIII cells. A single intravenous infusion of EGFRvIII-CART cells prolonged the survival of glioma-bearing mice when preceded by a lymphodepletion regimen with recurrent tumors displaying profound EGFRvIII loss. The addition of ONO-AE3-208 resulted in long-term survival in a fraction of CART-treated mice and those survivors demonstrated delayed growth of subcutaneously re-challenged both EGFRvIII+ and parental EGFRvIII− SB28.

Conclusion
Our new syngeneic CAR Tg mouse model can serve as a useful tool to address clinically relevant questions and develop future immunotherapeutic strategies.
Utilizing preclinical models to develop targeted therapies for rare central nervous system cancers
Authors: Arakaki Aleena K S , Szulzewsky Frank , Gilbert Mark R , Gujral Taranjit S , Holland Eric C 
Published: August 2021

Abstract
Patients with rare central nervous system (CNS) tumors typically have a poor prognosis and limited therapeutic options. Historically, these cancers have been difficult to study due to small number of patients. Recent technological advances have identified molecular drivers of some of these rare cancers which we can now use to generate representative preclinical models of these diseases. In this review, we outline the advantages and disadvantages of different models, emphasizing the utility of various in vitro and ex vivo models for target discovery and mechanistic inquiry and multiple in vivo models for therapeutic validation. We also highlight recent literature on preclinical model generation and screening approaches for ependymomas, histone mutated high-grade gliomas, and atypical teratoid rhabdoid tumors, all of which are rare CNS cancers that have recently established genetic or epigenetic drivers. These preclinical models are critical to advancing targeted therapeutics for these rare CNS cancers that currently rely on conventional treatments.
Phase I/II trial of vorinostat and radiation and maintenance vorinostat in children with diffuse intrinsic pontine glioma: A Children’s Oncology Group report
Authors: Su Jack M , Kilburn Lindsay B , Mansur David B , Krailo Mark , Buxton Allen , Adekunle Adesina , Gajjar Amar , Adamson Peter C , Weigel Brenda , Fox Elizabeth , Blaney Susan M , Fouladi Maryam 
Published: August 2021

Abstract

Background
A phase I/II trial of vorinostat (suberoylanilide hydroxamic acid), an oral histone deacetylase inhibitor, was conducted in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) through the Children’s Oncology Group (COG) to: 1) determine the recommended phase II dose (RP2D) of vorinostat given concurrently with radiation therapy; 2) document the toxicities of continuing vorinostat as maintenance therapy after radiation; and 3) to determine the efficacy of this regimen by comparing the risk of progression or death with a historical model from past COG trials.

Methods
Vorinostat was given once daily, Monday through Friday, during radiation therapy (54 Gy in 30 fractions), and then continued at 230 mg/m2 daily for a maximum of twelve 28-day cycles.

Results
Twelve patients enrolled in the phase I study; the RP2D of vorinostat given concurrently with radiation was 230 mg/m2/day, Monday through Friday weekly. The six patients enrolled at the RP2D and an additional 64 patients enrolled in the phase II study contributed to the efficacy assessment. Although vorinostat was well-tolerated, did not interrupt radiation therapy, and was permanently discontinued in only 8.6% of patients due to toxicities, risk for EFS-event was not significantly reduced compared with the target risk derived from historical COG data (P = 0.32; 1-sided). The 1-year EFS was 5.85% (95% CI 1.89–13.1%) and 1-year OS was 39.2% (27.8–50.5%).

Conclusions
Vorinostat given concurrently with radiation followed by vorinostat monotherapy was well tolerated in children with newly diagnosed DIPG but failed to improve outcome.
Discovery of carbon-based strongest and hardest amorphous material
Authors: Zhang Shuangshuang , Li Zihe , Luo Kun , He Julong , Gao Yufei , Soldatov Alexander V , Benavides Vicente , Shi Kaiyuan , Nie Anmin , Zhang Bin , Hu Wentao , Ma Mengdong , Liu Yong , Wen Bin , Gao Guoying , Liu Bing , Zhang Yang , Shu Yu , Yu Dongli , Zhou Xiang-Feng , Zhao Zhisheng , Xu Bo , Su Lei , Yang Guoqiang , Chernogorova Olga P , Tian Yongjun 
Published: August 2021

Abstract
Carbon is one of the most fascinating elements due to its structurally diverse allotropic forms stemming from its bonding varieties (sp, sp2 and sp3). Exploring new forms of carbon has been the eternal theme of scientific research. Herein, we report on amorphous (AM) carbon materials with a high fraction of sp3 bonding recovered from compression of fullerene C60 under high pressure and high temperature, previously unexplored. Analysis of photoluminescence and absorption spectra demonstrates that they are semiconducting with a bandgap range of 1.5–2.2 eV, comparable to that of widely used AM silicon. Comprehensive mechanical tests demonstrate that synthesized AM-III carbon is the hardest and strongest AM material known to date, and can scratch diamond crystal and approach its strength. The produced AM carbon materials combine outstanding mechanical and electronic properties, and may potentially be used in photovoltaic applications that require ultrahigh strength and wear resistance.
Search for $\alpha$ condensed states in $^{13}$C using $\alpha$ inelastic scattering
Authors: Inaba K , Sasamoto Y , Kawabata T , Fujiwara M , Funaki Y , Hatanaka K , Itoh K , Itoh M , Kawase K , Matsubara H , Maeda Y , Suda K , Sakaguchi S , Shimizu Y , Tamii A , Tameshige Y , Uchida M , Uesaka T , Yamada T , Yoshida H P 
Published: August 2021

AbstractWe searched for the $\alpha$ condensed state in $^{13}$C by measuring the $\alpha$ inelastic scattering at $E_\alpha = 388$ MeV at forward angles including 0$^\circ$. We performed a distorted-wave Born approximation calculation with the single-folding potential and multipole decomposition analysis to determine the isoscalar transition strengths in $^{13}$C. We found a bump structure around $E_x = 12.5$ MeV due to the isoscalar monopole ($IS0$) transition. A peak-fit analysis suggested that this bump consisted of several $1/2^-$ states. We propose that this bump is due to the mirror state of the 13.5 MeV state in $^{13}$N, which dominantly decays to the $\alpha$ condensed state in $^{12}$C. It was speculated that the $1/2^-$ states around $E_x = 12.5$ MeV were candidates for the $\alpha$ condensed state, but the $3\alpha + n$ orthogonality condition model suggests that the $\alpha$ condensed state is unlikely to emerge as the negative parity states. We also found two $1/2^+$ or $3/2^+$ states at $E_x = 14.5$ and 16.1 MeV excited with the isoscalar dipole ($IS1$) strengths. We suggest that the 16.1 MeV state is a possible candidate for the $\alpha$ condensed state predicted by the cluster model calculations on the basis of the good correspondence between the experimental and calculated level structures. However, the theoretical $IS1$ transition strength for this state is significantly smaller than the measured value. Further experimental information is strongly desired to establish the $\alpha$ condensed state in $^{13}$C.
Type II superstring field theory revisited
Authors: Kunitomo Hiroshi 
Published: August 2021

Abstract
We reconstruct a complete type II superstring field theory with $L_\infty$ structure in a symmetric way concerning the left- and right-moving sectors. Based on the new construction, we show again that the tree-level S-matrix agrees with that obtained using the first-quantization method. Not only is this a simple and elegant reconstruction, but it also enables the action to be mapped to that in the Wess–Zumino–Witten-like superstring field theory, which has not yet been constructed, and fills the only gap in that formulation.
Effectiveness of a Long-Term, Home-Based Aerobic Exercise Intervention on Slowing the Progression of Parkinson Disease: Design of the Cyclical Lower Extremity Exercise for Parkinson Disease II (CYCLE-II) Study
Authors: Alberts Jay L , Rosenfeldt Anson B , Lopez-Lennon Cielita , Suttman Erin , Jansen A Elizabeth , Imrey Peter B , Dibble Leland E 
Published: August 2021

Abstract

Objective
Previous short duration studies have demonstrated that high-intensity aerobic exercise improves aspects of motor and non-motor function in people with Parkinson disease (PwPD); however, the effectiveness of a long-term exercise intervention on slowing disease progression is unknown. The primary aim of this study is to determine the disease-altering effects of high-intensity aerobic exercise, administered on an upright stationary cycle, on the progression of PD. A secondary aim is to develop a prognostic model for 12-month changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) of PwPD undergoing an aerobic exercise intervention.

Methods
This pragmatic, multisite, single-rater blinded, randomized controlled trial will recruit PwPD from 2 large, urban, academic medical centers. Participants (N = 250 PwPD) will be randomized to (1) home-based aerobic exercise or (2) usual and customary care. Those in the aerobic exercise arm will be asked to complete in-home aerobic exercise sessions at 60% to 80% of heart rate reserve 3 times per week for 12 months utilizing a commercially available upright exercise cycle. The usual and customary care group will continue normal activity levels. Daily activity will be monitored for both groups throughout the 12-month study period. The primary outcome, both to assess disease-modifying response to aerobic exercise and for prognostic modeling in the aerobic exercise arm, is 12-month rate of change in the MDS-UPDRS III. Clinical and biomechanical measures will also be used to assess upper and lower extremity motor function as well as non-motor functions.

Impact
Should long-term aerobic exercise demonstrate disease-modifying capability, this study will provide evidence that “Exercise is Medicine” for PwPD. Further, the derived prognostic model will inform a patient-specific exercise prescription for PwPD and expected effects on PD progression.
The Active World of Passive Investing
Authors: Easley David , Michayluk David , O’Hara Maureen , Putniņš Tālis J 
Published: August 2021

Abstract
We investigate the new reality of exchange-traded funds (ETFs). We show that most ETFs are active investments in form (designed to generate alpha) or function (serve as building blocks of active portfolios). We define a new activeness index to capture these dimensions, finding that the cross-section of ETFs is now increasingly characterized by highly active investment vehicles. Active-in-form ETFs have positive flow-performance sensitivity, charge the highest fees among ETFs, and have high within-portfolio turnover. Active-in-function ETFs have more concentrated holdings, less within-portfolio turnover, but higher turnover in the secondary market. We show how more active ETFs are gaining market share over less active ETFs, leading to competitive fee pressure both within the ETF space and across the investment management industry. We suggest that the growing activeness of ETFs may assuage concerns about ETFs harming price discovery.
Knowledge networks in Brazil’s health sciences
Authors: Tatsch Ana Lúcia , Ruffoni Janaina , Botelho Marisa dos Reis A , Stefani Rafael 
Published: August 2021

AbstractThis study aims to analyze the network of interactions of Brazilian medical research groups, identifying key actors and their roles in generating and diffusing knowledge. Social network analysis was applied, with data from the Research Groups Directory Census of the National Council of Scientific and Technological Development, from 2016. The main results show (1) the central role of universities, public institutes, and university hospital research groups; (2) the importance of scientific infrastructure and research capability of scientists in knowledge production; (3) the minor role of the industry, denoting the fragility of university–industry interactions; (4) spatial concentration of network actors, mostly located in the south and southeast of Brazil; and (5) a great opportunity to expand flows and cooperation. Regarding these results, the recent budgetary cuts in science and technology resources since 2016 seem to be a misguided and detrimental strategy as these resources are essential for future technological and industrial development.
A Homolog of theArabidopsis TIME FOR COFFEEGene Is Involved in Nonhost Resistance to Wheat Stem Rust inBrachypodium distachyon
Authors: Della Coletta Rafael , Lavell Anastasiya A. , Garvin David F. 
Published: August 2021

Plants resist infection by pathogens using both preexisting barriers and inducible defense responses. Inducible responses are governed in a complex manner by various hormone signaling pathways. The relative contribution of hormone signaling pathways to nonhost resistance to pathogens is not well understood. In this study, we examined the molecular basis of disrupted nonhost resistance to the fungal species Puccinia graminis, which causes stem rust of wheat, in an induced mutant of the model grass Brachypodium distachyon. Through bioinformatic analysis, a 1-bp deletion in the mutant genotype was identified that introduces a premature stop codon in the gene Bradi1g24100, which is a homolog of the Arabidopsis thaliana gene TIME FOR COFFEE (TIC). In Arabidopsis, TIC is central to the regulation of the circadian clock and plays a crucial role in jasmonate signaling by attenuating levels of the transcription factor protein MYC2, and its mutational disruption results in enhanced susceptibility to the hemibiotroph Pseudomonas syringae. Our similar finding for an obligate biotroph suggests that the biochemical role of TIC in mediating disease resistance to biotrophs is conserved in grasses, and that the correct modulation of jasmonate signaling during infection by Puccinia graminis may be essential for nonhost resistance to wheat stem rust in B. distachyon.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Soybean Cyst Nematode Resistance Quantitative Trait Locus cqSCN-006 Alters the Expression of a γ-SNAP Protein
Authors: Butler Katelyn J. , Fliege Christina , Zapotocny Ryan , Diers Brian , Hudson Matthew , Bent Andrew F. 
Published: August 2021

Soybean cyst nematode (SCN) is the most economically damaging pathogen of soybean and host resistance is a core management strategy. The SCN resistance quantitative trait locus cqSCN-006, introgressed from the wild relative Glycine soja, provides intermediate resistance against nematode populations, including those with increased virulence on the heavily used rhg1-b resistance locus. cqSCN-006 was previously fine-mapped to a genome interval on chromosome 15. The present study determined that Glyma.15G191200 at cqSCN-006, encoding a γ-SNAP, contributes to SCN resistance. CRISPR/Cas9-mediated disruption of the cqSCN-006 allele reduced SCN resistance in transgenic roots. There are no encoded amino acid polymorphisms between resistant and susceptible alleles. However, other cqSCN-006-specific DNA polymorphisms in the Glyma.15G191200 promoter and gene body were identified, and we observed differing induction of γ-SNAP protein abundance at SCN infection sites between resistant and susceptible roots. We identified alternative RNA splice forms transcribed from the Glyma.15G191200 γ-SNAP gene and observed differential expression of the splice forms 2 days after SCN infection. Heterologous overexpression of γ-SNAPs in plant leaves caused moderate necrosis, suggesting that careful regulation of this protein is required for cellular homeostasis. Apparently, certain G. soja evolved quantitative SCN resistance through altered regulation of γ-SNAP. Previous work has demonstrated SCN resistance impacts of the soybean α-SNAP proteins encoded by Glyma.18G022500 (Rhg1) and Glyma.11G234500. The present study shows that a different type of SNAP protein can also impact SCN resistance. Little is known about γ-SNAPs in any system, but the present work suggests a role for γ-SNAPs during susceptible responses to cyst nematodes. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Transcriptomic links to muscle mass loss and declines in cumulative muscle protein synthesis during short‐term disuse in healthy younger humans
Authors: Willis Craig R. G. , Gallagher Iain J. , Wilkinson Daniel J. , Brook Matthew S. , Bass Joseph J. , Phillips Bethan E. , Smith Kenneth , Etheridge Timothy , Stokes Tanner , McGlory Chris , Gorissen Stefan H. M. , Szewczyk Nathaniel J. , Phillips Stuart M. , Atherton Philip J. 
Published: August 2021

AbstractMuscle disuse leads to a rapid decline in muscle mass, with reduced muscle protein synthesis (MPS) considered the primary physiological mechanism. Here, we employed a systems biology approach to uncover molecular networks and key molecular candidates that quantitatively link to the degree of muscle atrophy and/or extent of decline in MPS during short‐term disuse in humans. After consuming a bolus dose of deuterium oxide (D2O; 3 mL.kg−1), eight healthy males (22 ± 2 years) underwent 4 days of unilateral lower‐limb immobilization. Bilateral muscle biopsies were obtained post‐intervention for RNA sequencing and D2O‐derived measurement of MPS, with thigh lean mass quantified using dual‐energy X‐ray absorptiometry. Application of weighted gene co‐expression network analysis identified 15 distinct gene clusters (“modules”) with an expression profile regulated by disuse and/or quantitatively connected to disuse‐induced muscle mass or MPS changes. Module scans for candidate targets established an experimentally tractable set of candidate regulatory molecules (242 hub genes, 31 transcriptional regulators) associated with disuse‐induced maladaptation, many themselves potently tied to disuse‐induced reductions in muscle mass and/or MPS and, therefore, strong physiologically relevant candidates. Notably, we implicate a putative role for muscle protein breakdown‐related molecular networks in impairing MPS during short‐term disuse, and further establish DEPTOR (a potent mTOR inhibitor) as a critical mechanistic candidate of disuse driven MPS suppression in humans. Overall, these findings offer a strong benchmark for accelerating mechanistic understanding of short‐term muscle disuse atrophy that may help expedite development of therapeutic interventions.