bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photon regions and umbilic conditions in stationary axisymmetric spacetimes
Authors: Kobialko K. V. , Gal’tsov D. V. 
Published: June 2020

AbstractPhoton region (PR) in the strong gravitational field is defined as a compact region where photons can travel endlessly without going to infinity or disappearing at the event horizon. In Schwarzschild metric PR degenerates to the two-dimensional photon sphere $$r=3r_g/2$$r=3rg/2 where closed circular photon orbits are located. The photon sphere as a three-dimensional hypersurface in spacetime is umbilic (its second quadratic form is pure trace). In Kerr metric the equatorial circular orbits have different radii for prograde, $$r_p$$rp, and retrograde, $$r_r$$rr, motion (where r is Boyer–Lindquist radial variable), while for $$r_p<r<r_r$$rp<r<rr the spherical orbits with constant r exist which are no more planar, but filling some spheres. These spheres, however, do not correspond to umbilic hypersurfaces. In more general stationary axisymmetric spacetimes not allowing for complete integration of geodesic equations, the numerical integration show the existence of PR as well, but the underlying geometric structure was not fully identified so far. Here we suggest geometric description of PR in generic stationary axisymmetric spacetimes, showing that PR can be foliated by partially umbilic hypersurfaces, such that the umbilic condition holds for classes of orbits defined by the foliation parameter. New formalism opens a way of analytic description of PR in stationary axisymmetric spacetimes with non-separable geodesic equations.
Bottomonium spectrum with a Dirac potential model in the momentum space
Authors: Molina David , De Sanctis Maurizio , Fernández-Ramírez César , Santopinto Elena 
Published: June 2020

AbstractWe study the bottomonium spectrum using a relativistic potential model in the momentum space. This model is based on a complete one gluon exchange interaction with a momentum dependent screening factor to account for the effects due to virtual pair creation that appear close to the decay thresholds. The overall model does not make use of nonrelativistic approximations. We fit well established bottomonium states below the open bottom threshold and predict the rest of the spectrum up to$$\approx 11200$$≈11200MeV and$$J^{PC}=3^{--}$$JPC=3--. Uncertainties are treated rigorously and propagated in full to the parameters of the model using a Monte Carlo to identify if which deviations from experimental data can be absorbed into the statistical uncertainties of the models and which can be related to physics beyond the$$b\bar{b}$$bb¯picture, guiding future research. We get a good description of the spectrum, in particular the Belle measurement of the$$\eta _b(2S)$$ηb(2S)state and the$$\varUpsilon (10860)$$Υ(10860)and$$\chi _b(3P)$$χb(3P)resonances.
Edge probes of topological order
Authors: Heiblum Moty , Feldman D. E. 
Published: June 2020

According to the bulk-edge correspondence principle, the physics of the gapless edge in the quantum Hall effect determines the topological order in the gapped bulk. As the bulk is less accessible, the last two decades saw the emergence of several experimental techniques that invoke the study of the compressible edge. We review the properties of the edge, and describe several experimental techniques that include shot noise and thermal noise measurements, interferometry, and energy (thermal) transport at the edge. We pay special attention to the filling factor 5/2 in the first excited Landau level (in two-dimensional electron gas in GaAs), where experimental evidence of a non-Abelian topological order was found. A brief discussion is devoted to recent interferometry experiments that uncovered unexpected physics in the integer quantum Hall effect. The article also addresses the theory of edge states, for systems with Abelian and non-Abelian topological orders.
Study of the thermophysical kinetics of additional concrete samples
Authors: Akbarova S. M. , Gahramanov S. H. , Mirzayeva D. M. 
Published: June 2020

In this work, Fix 1211 addition has been used in different amount in the iron mix. The samples prepared have been used thermically in the temperature 77[Formula: see text]C in normal atmosphere condition. The samples thermically developed have been thermically analyzed with the constant 5[Formula: see text]C/min of 20 ml/min argon gas from 30[Formula: see text]C up to 900[Formula: see text]C. Thermo-physical mechanisms have been researched in the cement, sand and road metal with the thermogravimetric (TG) and Differential Scanning Calorimetry (DSC) analysis. Mass kinetics, activation energy and special heat capacity have been researched for different temperature intervals. The decomposition mechanism of the mass in stages and the speed of decomposition is equal to the cost of the heat flow. The mass loss has been determined in 6.99 mg under the first code, 5.82 mg under the second code, 5.63 mg under the third code, 4.65 mg under the fourth code in [Formula: see text]C temperature interval. In addition, it has been researched that the activation energy has been changed between 0.56–0.80 eV and 0.23–0.36 eV under each code and phase passage.
Repeated Nucleic Acid Tests Are Necessary for Early Diagnosis of Atypical COVID-19: A Case Report
Authors: Qu Lihong , Xiong Wujun , Fan Chenghui , Kang Sheng 
Published: June 2020

In Wuhan, China, the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported on December 8, 2019. The patient’s symptoms included fever, coughing and breathing difficulties. According to the sixth China version of 2019 coronavirus disease (COVID-19) diagnostic criteria, some patients with COVID-19 may present atypical symptoms and have negative nucleic acid tests (NATs), possibly leading to misdiagnosis and viral transmission.Our patient was a 29-year-old woman who complained of a three-day history of nasal obstruction, and no fever, coughing or breathing difficulties were noted. Physical examination revealed no obvious signs of pneumonia. On January 16, 2020, the patient flew from Wuhan to Germany for a business trip and returned to Shanghai on January 28, a passenger on her flight was tested positive for SARS-CoV-2 later. Although two consecutive NATs performed at an interval of 24 h were negative, considering her direct contact with a SARS-CoV-2-infected individual, a 64-slice computed tomography (CT) scan showed a few scattered ground-glass nodules in the left lung, suggesting possible viral pneumonia. Given the clinical characteristics, epidemiological records, CT findings and a third positive NAT, our patient was diagnosed with COVID-19.The combination of history of epidemiology, clinical symptom, lung CT scan and routine blood test will improve the clinical diagnosis of asymptomatic COVID-19, but the early diagnosis of COVID-19 can be confirmed only by the repeated NATs.
A history of Clojure
Authors: Hickey Rich 
Published: June 2020

Clojure was designed to be a general-purpose, practical functional language, suitable for use by professionals wherever its host language, e.g., Java, would be. Initially designed in 2005 and released in 2007, Clojure is a dialect of Lisp, but is not a direct descendant of any prior Lisp. It complements programming with pure functions of immutable data with concurrency-safe state management constructs that support writing correct multithreaded programs without the complexity of mutex locks.
Clojure is intentionally hosted, in that it compiles to and runs on the runtime of another language, such as the JVM. This is more than an implementation strategy; numerous features ensure that programs written in Clojure can leverage and interoperate with the libraries of the host language directly and efficiently.
In spite of combining two (at the time) rather unpopular ideas, functional programming and Lisp, Clojure has since seen adoption in industries as diverse as finance, climate science, retail, databases, analytics, publishing, healthcare, advertising and genomics, and by consultancies and startups worldwide, much to the career-altering surprise of its author.
Most of the ideas in Clojure were not novel, but their combination puts Clojure in a unique spot in language design (functional, hosted, Lisp). This paper recounts the motivation behind the initial development of Clojure and the rationale for various design decisions and language constructs. It then covers its evolution subsequent to release and adoption.
The origins of Objective-C at PPI/Stepstone and its evolution at NeXT
Authors: Cox Brad J. , Naroff Steve , Hsu Hansen 
Published: June 2020

The roots of Objective-C began at ITT in the early 1980s in a research group led by Tom Love investigating improving programmer productivity by an order of magnitude, a concern motivated by the perceived "software crisis" articulated in the late 1960s. In 1981, Brad Cox, a member of this group, began to investigate Smalltalk and object-oriented programming for this purpose, but needed a language compatible with the Unix and C environments used by ITT. That year, Cox quickly wrote up the Object-Oriented Pre-Compiler (OOPC) that would translate a Smalltalk-like syntax into C.
Love felt there was a market for object-oriented solutions that could coexist with legacy languages and platforms, and after a brief stint at Schlumberger-Doll, co-founded with Cox Productivity Products International (PPI), later renamed as Stepstone, to pursue this. At PPI, Cox developed OOPC into Objective-C. Cox saw Objective-C as a crucial link in his larger vision of creating a market for "pre-fabricated" software components ("software-ICs"), which could be bought off the shelf and which, Cox believed, would unleash a "software industrial revolution."
Steve Naroff joined Stepstone in 1986 as Steve Jobs' NeXT Computer became an important customer for Objective-C, as it was being used in its NeXTSTEP operating system. Naroff became the primary Stepstone developer addressing NeXT's issues with Objective-C, solving a key fragility problem preventing NeXT from deploying forwards-compatible object libraries. Impressed with NeXT, Naroff left Stepstone for NeXT in 1988, and once there, added Objective-C support to Richard Stallman's GNU GCC compiler, which NeXT was using as its C compiler, removing the need to use Stepstone's ObjC to C translator. Over the next several years, Naroff and others would add significant new features to Objective-C, such as "categories," "protocols," and the ability to mix in C++ code. When Stepstone folded in 1994, all rights to Objective-C were acquired by NeXT. This eventually transferred to Apple when NeXT was acquired by Apple in 1997. Objective-C became the basis for Apple's Mac OS X and then iOS platforms, and Naroff and others at Apple added additional features to the language in the late 2000s as the iPhone App Store greatly expanded Objective-C's user base.
The evolution of Smalltalk: from Smalltalk-72 through Squeak
Authors: Ingalls Daniel 
Published: June 2020

This paper presents a personal view of the evolution of six generations of Smalltalk in which the author played a part, starting with Smalltalk-72 and progressing through Smalltalk-80 to Squeak and Etoys. It describes the forces that brought each generation into existence, the technical innovations that characterized it, and the growth in understanding of object-orientation and personal computing that emerged. It summarizes what that generation achieved and how it affected the future, both within the evolving group of developers and users, and in the outside world.
The early Smalltalks were not widely accessible because they ran only on proprietary Xerox hardware; because of this, few people have experience with these important historical artifacts. To make them accessible, the paper provides links to live simulations that can be run in present-day web browsers. These simulations offer the ability to run pre-defined scripts, but also allow the user to go off-script, browse the details of the implementation, and try anything that could be done in the original system. An appendix includes anecdotal and technical aspects of how examples of each generation of Smalltalk were recovered, and how order was teased out of chaos to the point that these old systems could be brought back to life.
Exploiting Errors for Efficiency
Authors: Stanley-Marbell Phillip , Alaghi Armin , Carbin Michael , Darulova Eva , Dolecek Lara , Gerstlauer Andreas , Gillani Ghayoor , Jevdjic Djordje , Moreau Thierry , Cacciotti Mattia , Daglis Alexandros , Jerger Natalie Enright , Falsafi Babak , Misailovic Sasa , Sampson Adrian , Zufferey Damien 
Published: June 2020

When a computational task tolerates a relaxation of its specification or when an algorithm tolerates the effects of noise in its execution, hardware, system software, and programming language compilers or their runtime systems can trade deviations from correct behavior for lower resource usage. We present, for the first time, a synthesis of research results on computing systems that only make as many errors as their end-to-end applications can tolerate. The results span the disciplines of computer-aided design of circuits, digital system design, computer architecture, programming languages, operating systems, and information theory. Rather than over-provisioning the resources controlled by each of these layers of abstraction to avoid errors, it can be more efficient to exploit the masking of errors occurring at one layer and thereby prevent those errors from propagating to a higher layer.
We demonstrate the potential benefits of end-to-end approaches using two illustrative examples. We introduce a formalization of terminology that allows us to present a coherent view across the techniques traditionally used by different research communities in their individual layer of focus. Using this formalization, we survey tradeoffs for individual layers of computing systems at the circuit, architecture, operating system, and programming language levels as well as fundamental information-theoretic limits to tradeoffs between resource usage and correctness.
Nivolumab in Patients with Advanced Platinum-resistant Urothelial Carcinoma: Efficacy, Safety, and Biomarker Analyses with Extended Follow-up from CheckMate 275
Authors: Galsky Matthew D. , Saci Abdel , Szabo Peter M. , Han G. Celine , Grossfeld Gary , Collette Sandra , Siefker-Radtke Arlene , Necchi Andrea , Sharma Padmanee 
Published: June 2020

AbstractPurpose:We report efficacy and safety with extended follow-up, and exploratory biomarker analyses from the phase II CheckMate 275 trial to identify biomarkers of response to nivolumab in platinum-resistant metastatic or unresectable urothelial carcinoma (mUC).Patients and Methods:Patients received nivolumab 3 mg/kg once every 2 weeks until disease progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was objective response rate (ORR) per blinded independent review committee (BIRC; using RECIST v1.1) in all treated patients and by tumor PD-L1 expression. Key secondary endpoints were progression-free survival (PFS) per BIRC using RECIST v1.1 and overall survival (OS) in all patients and by PD-L1 expression. Exploratory endpoints included safety and biomarker analyses of tumor mutational burden (TMB), PD-L1, and previously identified mutational signatures.Results:Of 270 treated patients, 139 had evaluable TMB. With 33.7 months' minimum follow-up, ORR per BIRC, median PFS, and median OS [95% confidence interval (CI)] in all treated patients were 20.7% (16.1–26.1), 1.9 months (1.9–2.3), and 8.6 months (6.1–11.3), respectively. No new safety signals were identified. Higher TMB was associated (P &lt; 0.05) with improved ORR [OR (95% CI): 2.13 (1.26–3.60)], PFS [HR: 0.75 (0.61–0.92)], and OS [HR: 0.73 (0.58–0.91)]. TMB combined with PD-L1 better predicted ORR, PFS, and OS than PD-L1 alone. Higher mutational signature 2 score was associated with better OS but did not improve the predictive value of TMB.Conclusions:These results support the durable antitumor activity of nivolumab and suggest that TMB may enrich for better response in mUC. Future studies of TMB/PD-L1 as biomarkers for response to nivolumab in randomized trials are warranted.See related commentary by Swami et al., p. 5059
A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408
Authors: Evens Andrew M. , Hong Fangxin , Habermann Thomas M. , Advani Ranjana H. , Gascoyne Randy D. , Witzig Thomas E. , Quon Andrew , Ranheim Erik A. , Ansell Stephen M. , Cheema Puneet Singh , Dy Philip A. , O'Brien Timothy E. , Winter Jane N. , Cescon Terrence P. , Chang Julie E. , Kahl Brad S. 
Published: June 2020

Abstract

Purpose:
We sought to improve upon frontline bendamustine/rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL).

Patients and Methods:
Patients were randomized to BR induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with rituximab maintenance (BR-LR). Dual primary objectives were complete remission (CR) rate and 1-year disease-free survival (DFS); 289 patients enrolled (NCT01216683).

Results:
For induction, 92%, 87%, and 86% of patients randomized to BR-R, BVR-R, or BR-LR received six cycles, respectively. CR rate with BR versus BVR induction was 62% versus 75%, respectively (P = 0.04). One-year DFS rates with BR-R versus BR-LR were 85% versus 67%, respectively (P = 0.0009). This was due to an imbalance in CR rates post-BR induction and discontinuation due to adverse events (AEs). The most common grade 3–4 AEs for BVR versus BR were neutropenia and sensory neuropathy (12% vs &lt;1%); 83% of the latter occurred with intravenous bortezomib. The most common grade 3–4 AEs related to LR versus rituximab maintenance were neutropenia 66% versus 21%, respectively (P &lt; 0.0001), and febrile neutropenia 10% versus 2%, respectively (P = 0.05). The overall treatment-related mortality was 1.4%. With 5-year median follow-up, 3-year PFS rates for BR-R, BVR-R, and BR-LR were 77%, 82%, and 76%, respectively (P = 0.36) with OS rates of 87%, 90%, and 84%, respectively (P = 0.79). For prognostication, CR rate and POD-24 were associated with survival.

Conclusions:
Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction is recommended in untreated FL.
B55α/PP2A Limits Endothelial Cell Apoptosis During Vascular Remodeling
Authors: Ehling Manuel , Celus Ward , Martín-Pérez Rosa , Alba-Rovira Roser , Willox Sander , Ponti Donatella , Cid Maria C. , Jones Elizabeth A.V. , Di Conza Giusy , Mazzone Massimiliano 
Published: June 2020

Rationale:
How endothelial cells (ECs) migrate and form an immature vascular plexus has been extensively studied. Yet, mechanisms underlying vascular remodeling remain poorly established. A better understanding of these processes may lead to the design of novel therapeutic strategies complementary to current angiogenesis inhibitors.

Objective:
Starting from our previous observations that PP2A (protein phosphatase 2) regulates the HIF (hypoxia-inducible factor)/PHD-2 (prolyl hydroxylase 2)-constituted oxygen machinery, we hypothesized that this axis could play an important role during blood vessel formation, tissue perfusion, and oxygen restoration.

Methods and Results:
We show that the PP2A regulatory subunit B55α is at the crossroad between vessel pruning and vessel maturation. Blood vessels with high B55α counter cell stress conditions and thrive for stabilization and maturation. When B55α is inhibited, ECs cannot cope with cell stress and undergo apoptosis, leading to massive pruning of nascent blood vessels. Mechanistically, we found that the B55α/PP2A complex restrains PHD-2 activity, promoting EC survival in a HIF-dependent manner, and furthermore dephosphorylates p38, altogether protecting ECs against cell stress occurring, for example, during the onset of blood flow. In tumors, EC-specific B55α deficiency induces pruning of immature-like tumor blood vessels resulting in delayed tumor growth and metastasis, without affecting nonpathological vessels. Consistently, systemic administration of a pan-PP2A inhibitor disrupts vascular network formation and tumor progression in vivo without additional effects on B55α-deficient vessels.

Conclusions:
Our data underline a unique role of the B55α/PP2A phosphatase complex in vessel remodeling and suggest the use of PP2A-inhibitors as potent antiangiogenic drugs targeting specifically nascent blood vessels with a mode-of-action complementary to VEGF-R (vascular endothelial growth factor receptor)-targeted therapies.

Graphical Abstract:
A graphical abstract is available for this article.
Epigenomes of Human Hearts Reveal New Genetic Variants Relevant for Cardiac Disease and Phenotype
Authors: Tan Wilson Lek Wen , Anene-Nzelu Chukwuemeka George , Wong Eleanor , Lee Chang Jie Mick , Tan Hui San , Tang Sze Jing , Perrin Arnaud , Wu Kan Xing , Zheng Wenhao , Ashburn Robert John , Pan Bangfen , Lee May Yin , Autio Matias Ilmari , Morley Michael P. , Tam Wai Leong , Cheung Christine , Margulies Kenneth B. , Chen Leilei , Cappola Thomas P. , Loh Marie , Chambers John , Prabhakar Shyam , Foo Roger S.Y. , Assa Solmaz , Ellinor Patrick , Felix Janine , van der Harst Pim , Meder Benjamin , Smith Gustav J. , Tappu Rewati 
Published: June 2020

Rationale:
Identifying genetic markers for heterogeneous complex diseases such as heart failure is challenging and requires prohibitively large cohort sizes in genome-wide association studies to meet the stringent threshold of genome-wide statistical significance. On the other hand, chromatin quantitative trait loci, elucidated by direct epigenetic profiling of specific human tissues, may contribute toward prioritizing subthreshold variants for disease association.

Objective:
Here, we captured noncoding genetic variants by performing epigenetic profiling for enhancer H3K27ac chromatin immunoprecipitation followed by sequencing in 70 human control and end-stage failing hearts.

Methods and Results:

We have mapped a comprehensive catalog of 47 321 putative human heart enhancers and promoters. Three thousand eight hundred ninety-seven differential acetylation peaks (FDR [false discovery rate], 5%) pointed to pathways altered in heart failure. To identify cardiac histone acetylation quantitative trait loci (haQTLs), we regressed out confounding factors including heart failure disease status and used the G-SCI (Genotype-independent Signal Correlation and Imbalance) test

1

to call out 1680 haQTLs (FDR, 10%). RNA sequencing performed on the same heart samples proved a subset of haQTLs to have significant association also to gene expression (expression quantitative trait loci), either in
cis
(180) or through long-range interactions (81), identified by Hi-C (high-throughput chromatin conformation assay) and HiChIP (high-throughput protein centric chromatin) performed on a subset of hearts. Furthermore, a concordant relationship between the gain or disruption of TF (transcription factor)-binding motifs, inferred from alternative alleles at the haQTLs, implied a surprising direct association between these specific TF and local histone acetylation in human hearts. Finally, 62 unique loci were identified by colocalization of haQTLs with the subthreshold loci of heart-related genome-wide association studies datasets.

Conclusions:

Disease and phenotype association for 62 unique loci are now implicated. These loci may indeed mediate their effect through modification of enhancer H3K27 acetylation enrichment and their corresponding gene expression differences (bioRxiv:
https://doi.org/10.1101/536763
).

Graphical Abstract:
A graphical abstract is available for this article.