bluuebunny/crossref_metadata_2025 huggingface dataset:
Relaxion dark matter from stochastic misalignment
Authors: Chatrchyan Aleksandr , Servant Géraldine
Published: June 2023

Cosmological relaxation of the electroweak scale via Higgs-axion interplay, named as relaxion mechanism, provides a dynamical solution to the Higgs mass hierarchy. In the original proposal by Graham, Kaplan and Rajendran, the relaxion abundance today is too small to explain the dark matter of the universe because of the high suppression of the misalignment angle after inflation. It was then realised by Banerjee, Kim and Perez that reheating effects can displace the relaxion, thus enabling it to account for the dark matter abundance from the misalignment mechanism. However, this scenario is realised in a limited region of parameter space to avoid runaway. We show that in the regime where inflationary fluctuations dominate over the classical slow-roll, the “stochastic misalignment” of the field due to fluctuations can be large. We study the evolution of the relaxion after inflation, including the high-temperature scenario, in which the barriers of the potential shrink and destabilise temporarily the local minimum. We open new regions of parameter space where the relaxion can naturally explain the observed dark matter density in the universe, towards larger coupling, larger mass, larger mixing angle, smaller decay constant, as well as larger scale of inflation.
Measurement science meets the reproducibility challenge
Authors: Possolo Antonio
Published: June 2023

Measurement science is particularly well equipped not only to meet reproducibility challenges arising within the field of metrology, but also to suggest strategies and best practices for how such challenges can be met in other fields. This contribution illustrates three such challenges, in three different fields, and proposes ways to address them that can supplement the only way in which reproducibility challenges in science can be resolved definitively: by validated scientific advances that point toward the truth. The first example concerns a large interlaboratory, international comparison of the measurement of the mass fraction of silica in a granite reference material, using classical methods of wet analytical chemistry, carried out in the 1940s. The results delivered a shock to analysts worldwide about the state of the art at the time. The challenge was magnified by the fact that none of the measured values was qualified with an evaluation of measurement uncertainty. We offer an approach developed by Andrew Rukhin from NIST, for how to compute a meaningful consensus value in such case, and explain how the associated uncertainty can be characterized. The second example is about the currently hot topic of the Hubble tension, which refers to the mutual inconsistency of the measurement results, obtained by different methods, for the Hubble-Lemaître constant, which expresses the rate of expansion of the Universe. We suggest that such tension can be quantified in terms of the dark uncertainty that figures as a parameter in a laboratory random effects model, thus providing an objective metric whereby progress toward resolving such tension can be gauged. The third example discusses two sources of lack of reproducibility: on the one hand, the fact that different laboratories produced strikingly discrepant values for the mass fraction of arsenic in kudzu; on the other hand, that different models can be fitted to these data, each producing its own set of results. Here we use a Bayesian model selection criterion to choose one from among four models that are natural candidates to address this double reproducibility challenge. This third example also affords us the opportunity to deflate two widespread myths: that one needs at least four observations to obtain a Bayesian evaluation of standard uncertainty, and that sample standard deviations of small samples are systematically too small.
Characteristics of a real-time ensemble time scale corrected by the KRISS-PSFS using a reduced Kalman filter (Kred) algorithm
Authors: Lee Ho Seong , Kwon Taeg Yong , Park Sang Eon , Lee Young Kyu , Yang Sung-hoon , Yu Dai-Hyuk , Heo Myoung-Sun , Kim Huidong , Park Chang Yong , Lee Won-Kyu
Published: June 2023

An ensemble time, which is indicated by TA (temps atomique, in French), was generated every minute by combining four active hydrogen masers with the reduced Kalman filter (Kred) algorithm. The TA frequency was averaged over 12 h and then the mean frequency was steered to the primary and secondary frequency standards developed by KRISS with a micro-phase stepper (MPS). The steered and physically realized TA frequency is called KRISS ensemble time (KET). We investigated the frequency-state estimate outputted from the Kred algorithm and the control signal applied to the MPS, according to the abnormal temperature change of the room where the hydrogen masers were placed. When the frequency of the TA was corrected by the KRISS-F1, the Allan deviation of KET was 1.72 × 10−15 at the average time τ = 1 d, and the variation of [UTC–KET] was stable within 2 ns for 75 d.
Measurements and modeling of type-I and type-II ELMs heat flux to the DIII-D divertor
Authors: Perillo R. , Boedo J.A. , Lasnier C.J. , Pitts R.A. , Brank M. , Bykov I. , Coburn J.D. , Glass F. , Marini C. , Osborne T. , Riding M. , Rudakov D.L. , Watkins J.G. , Zeng L.
Published: June 2023

Type-I and type-II edge-localized-modes (ELMs) heat flux profiles measured at the DIII-D divertor feature a peak in the vicinity of the strike-point and a plateau in the scrape-off-layer (SOL), which extends to the first wall. The plateau is present in attached and detached divertors and it is found to originate with plasma bursts upstream in the SOL. The integrated ELM heat flux is distributed at ∼65% in the peak and ∼35% in this plateau. The parallel loss model, currently used at ITER to predict power loads to the walls, is benchmarked using these results in the primary and secondary divertors with unprecedented constraints using experimental input data for ELM size, radial velocity, energy, electron temperature and density, heat flux footprints and number of filaments. The model can reproduce the experimental near-SOL peak within ∼20%, but cannot match the SOL plateau. Employing a two-component approach for the ELM radial velocity, as guided by intermittent data, the full radial heat flux profile can be well matched. The ELM-averaged radial velocity at the separatrix, which explains profile widening, increases from ∼0.2 km s−1 in attached to ∼0.8 km s−1 in detached scenarios, as the ELM filaments’ path becomes electrically disconnected from the sheath at the target. The results presented here indicate filaments fragmentation as a possible mechanism for ELM transport to the far-SOL and provide evidence on the beneficial role of detachment to mitigate ELM flux in the divertor far-SOL. However, these findings imply that wall regions far from the strike points in future machines should be designed to withstand significant heat flux, even for small-ELM regimes.
Potential of Ultra-High-Performance Concrete (UHPC) for Refurbishment of Bridges
Authors: Fehling Ekkehard , Thiemicke Jenny
Published: June 2023

In many countries, the bridge infrastructure suffers from damaged bridges that need to be rehabilitated or replaced. This means that the state or the institutions responsible for this must make extensive investments. Are there other ways to address the problems caused by the damaging effects of de-icing agents, by fatigue due to high vehicle loads and frequencies on the load side or by lack of fatigue strength of, for example, orthotropic bridge decks? Yes, UHPC surface courses can be used as a protective barrier against aggressive substances such as chlorides. They can also be load-bearing and contribute to improved bearing capacity while providing durability. In addition, a single layer can replace the foundation of multiple layers required for sealing and trafficability. The following article shows the potential of such UHPC layers for improving existing bridges, be they concrete or steel bridges.
Nonlinear finite element analyses of reinforced concrete beam-column joints subjected to cyclic loading
Authors: Handoko J , Gunawan A , Chandra J , Wibowo H
Published: June 2023

Interaction of forces and moments in a beam-column joint is complex and most of the time nonlinear. Thus, a simple, global model is insufficient to estimate the performance and behavior of the joint. Results from several nonlinear finite element analyses of beam-column joints using VecTor2 are presented herein. Four interior and two exterior beam-column joint models with three different types of failure were studied. The analysis results in terms of force-drift ratio curves and crack patterns were then compared to the experimental results. In general, the results obtained from VecTor2 were satisfactory, but in some cases the program could not accurately capture the strength degradation observed in the specimen with joint shear failure. Moreover, the crack patterns were not accurately captured. Nevertheless, VecTor2 can still estimate the peak forces well for all specimens in this study.
Mechanical behaviours of cellular lightweight concrete using finite element analysis
Authors: Suryanita Reni , Maizir Harnedi , Saputra Hari
Published: June 2023

Cellular Lightweight Concrete (CLC) is a concrete brick with a density lighter than concrete bricks. The efficiency of the use and quality of CLC can be determined by analysing mechanical behaviour using the finite element method. The purpose of this study is to analyse the mechanical behaviour of lightweight concrete using the finite element method. Analysis of mechanical behaviour using LUSAS finite element software. The CLC model used admixture materials of silica foam, palm oil fly ash (POFA) and lime (CaCO3). The study resulted in the difference between the numeric and experimental analysis being less than 10%. The most considerable deformation occurred at the top of the CLC model based on the deformation contour distribution. The most significant stress and strain contours distribution occurred at the CLC model’s bottom. The controlled load of 6 kN to 60 kN causes an increase in the mechanical behaviour of CLC. The most considerable deformation occurred when the maximum load on the CLC model with a silica fume mixture was 9.239 mm. The stress of the CLC model is 1.148 N/mm2, and the most significant strain occurred in CLC with silica fume admixture with a CLC weight of 0.038. Thus, the finite element method can be used as a comparison of laboratory test results to determine the mechanical behaviour of CLC.
Accident prevention in a highly occupied building through safety audit: a readiness perspective in university buildings
Authors: Hermawan F , Pratiwi A N , Susanto T , Hatmoko J U D
Published: June 2023

Potential accidents can occur at any time, including educational activities at a university. Twenty-four cases of accidents at universities in Indonesia, in the form of collapsing building components and fires, have been recorded in the last decade. There is a need for colleges to be ready to implement a Construction Safety Management System in the buildings where educational activities take place. There are two aspects to construction safety in public buildings: the engineering aspect and the aspect of safety management and occupational health. This research aims to assess and analyse the readiness to apply construction safety in a building with large occupancy. The research method uses a case study of a building in the civil engineering department of a university in Indonesia. Data collection comprised field surveys, semi-structured interviews and the collection of drawings and documents regarding the management of occupational safety and health in 2020-2021. The results show that the site studied was mediocre, in terms of implementing a construction safety management system. Although the physical condition of the building is good, other indicators, such as building documents and the application of occupational health and safety, fall into the ‘lack of application’ category.
Corrosivity of water for concrete and metal water resources infrastructure with modification of the DIN Method and Langelier Saturation Index of Metcalf and Eddy
Authors: Lestari Devita Satya , Sukamta  , Sari Yunitta Chandra
Published: June 2023

Corrosion or rust is an endless problem, both in Indonesia and in the world. This is so because corrosion or rust is very detrimental, especially if it occurs in water infrastructure, particularly one built from concrete and metal. Corrosion is a decrease in material quality due to a reaction with the environment. The kinds of losses incurred if corrosion occurs in the infrastructure of water resources include reservoir collapse due to the acceleration of corrosion in the dam, damage to the turbine, and damage to the irrigation gates. This research was conducted to determine level of corrosivity water to water infrastructure built from concrete and metal in 9 (nine) reservoirs. The primary data consist of water quality parameters, determined by sampling the water. The storage and preservation methods of the water samples were done in accordance with Indonesian National Standard Number 6989.57:2008. Water quality was tested by an accredited laboratory. Corrosivity of water for metal and concrete infrastructure was calculated using Metcalf and Eddy formula (2003) and the modification of the DIN 4030 method (2008), respectively. The results of the calculation with Metcalf and Eddy’s LSI (2003) show that the water corrosivity in the 9 (nine) reservoirs had the potential to damage the metal infrastructure, ranging from mild to severe corrosion and lime/crust formation. Based on the modification of the DIN 4030 method (2008), the water in 7 (seven) reservoirs did not have the potential to damage concrete infrastructure, but the water in 2 (two) reservoirs had the potential to damage the concrete infrastructure from mild to moderate level.
Liquefaction severity assessment for the Anutapura Medical Center Area of Palu-Indonesia
Authors: Simatupang Minson , Edwin Romy Suryaningrat , Sulha
Published: June 2023

A liquefaction hazard assessment for a particular location is important to reduce disasters that may occur in the future. The liquefaction severity assessment for the Anutapura Medical Centre region of Palu-Indonesia was carried out on various pairs between peak ground surface acceleration and earthquake magnitude. It was conducted by first determining the factor of safety for each existing soil layer and applying the formulation prepared by Iwasaki to measure Liquefaction Potential for the entire soil column. The possible severity of liquefaction at these locations was compared based on the limits set by the respective theories of Iwasaki and Papathanassiou. The results showed that the Anutapura Medical Centre location was very susceptible to liquefaction events with a very high potential level of ground surface damage based on the Iwasaki boundary line. The above-mentioned severity by Papathanassiou limits ranges from high to very high.
Additional Lateral Soil Pressure on Soil due to The Vehicle at a Constant Speed
Authors: Handiman Iman , Redana I Wayan , Hidayanti Anisa Maria , Sudarsana I Ketut
Published: June 2023

On roads that cross the slope is often required evaluation of the need for retaining slope construction (road). In the design of the construction, one of the main factors that must be known is the amount of horizontal ground pressure that occurs. The amount of ground pressure consists of the ground pressure it self and the pressure due to other loads such as vehicles passing on it. The horizontal pressure due to constant and stationary loads is different from the horizontal pressure due to a running vehicle. This study was conducted to determine how the additional influence of horizontal pressure that occurs due to the vehicle through on it. A model (vehicle) is simulated to move at a constant speed along a sensor-Fed trajectory at a predetermined position. Instrumentation results show that the additional pressure that occurs in the form of pressure bubbles is similar to the pressure due to stationary and constant vertical loads. Test results for low-speed loads below 10 km/hrs showed the greatest horizontal pressure that occurs at a depth of 0.5 m and a distance of 0.5 m from the instrumentation. A comparison using the Boussinesq equation using the same load, shows that the maximum horizontal pressure that occurs is still relatively smaller than the additional lateral pressure due to static load.
Photon statistics and quantum phase distribution for coherent optical links in the presence of phase noise from both the laser source and the RF oscillator, and dispersion
Authors: Pratap Rana , Ramachandran Harishankar
Published: June 2023

A model of photon statistics and quantum phase distribution is analyzed for coherent optical communication links in the presence of quantum phase noise, dispersion and phase noise of the radio-frequency (RF) oscillator using an in-line optical amplifier. The quantum analysis of a dual drive Mach–Zehnder modulator and the quantum transfer function for an optical field mode across an in-line amplifier is performed by taking into account both the quantum and the classical phase noises. The resulting photon statistics are compared with the semiclassical model. We analyze the quantum phase distribution by considering the Wigner quasiprobability distribution for a coherent optical link. Here, we investigate the broadening of the quantum phase distribution due to quantum phase noise of the laser, the dispersive optical fiber, the phase noise of the RF oscillator and the inevitable noise coefficient of the optical amplifier for arbitrary amplified spontaneous emission (ASE) field modes. We analytically investigate the quantum analog to the bit error rate (BER) as a function of the laser’s linewidth, the linewidth of the RF oscillator and chromatic dispersion. The results of quantum models are compared with the semiclassical model. Quantum treatment of both the BER and variance is found to agree with prior results for a single-mode ASE field in the absence of phase noise but deviate when the effect of phase noise is considered. Including phase noise effects in the amplitude in the semiclassical treatment of the BER yields a new semiclassical expression that agrees with quantum expressions of machine precision for single-mode ASE fields.
Graphene nanoribbons with hBN passivated edges grown by high-temperature molecular beam epitaxy
Authors: Bradford Jonathan , Cheng Tin S , James Tyler S S , Khlobystov Andrei N , Mellor Christopher J , Watanabe Kenji , Taniguchi Takashi , Novikov Sergei V , Beton Peter H
Published: June 2023

Integration of graphene and hexagonal boron nitride (hBN) in lateral heterostructures has provided a route to broadly engineer the material properties by quantum confinement of electrons or introduction of novel electronic and magnetic states at the interface. In this work we demonstrate lateral heteroepitaxial growth of graphene nanoribbons (GNRs) passivated by hBN using high-temperature molecular beam epitaxy (HT-MBE) to grow graphene in oriented hBN trenches formed ex-situ by catalytic nanoparticle etching. High-resolution atomic force microscopy (AFM) reveals that GNRs grow epitaxially from the etched hBN edges, and merge to form a GNR network passivated by hBN. Using conductive AFM we probe the nanoscale electrical properties of the nanoribbons and observe quasiparticle interference patterns caused by intervalley scattering at the graphene/hBN interface, which carries implications for the potential transport characteristics of hBN passivated GNR devices.
Superlinear stochastic heat equation on ℝ^{𝕕}
Authors: Chen Le , Huang Jingyu
Published: June 2023

In this paper, we study the stochastic heat equation (SHE) on

R

d

\mathbb {R}^d

subject to a centered Gaussian noise that is white in time and colored in space. We establish the existence and uniqueness of the random field solution in the presence of locally Lipschitz drift and diffusion coefficients, which can have certain superlinear growth. This is a nontrivial extension of the recent work by Dalang, Khoshnevisan and Zhang [Ann. Probab. 47 (2019), pp. 519–559], where the one-dimensional SHE on

[
0
,
1
]

[0,1]

subject to space-time white noise has been studied.
Towards standardization of positron emission testing with computed tomography myocardial perfusion volumes and left ventricular ejection fraction: comparison with cardiac MRI
Authors: Dong Tiffany A , Abadie Bryan Q , Hutt Centeno Erika , Jellis Christine L , Cremer Paul C , Jaber Wael A
Published: June 2023

Gated positron emission testing with computed tomography (PET-CT) yields left ventricular (LV) volume analysis along with perfusion analysis. The correlation between PET-CT volumes and cardiac magnetic resonance imaging (CMR) volumes remains unknown. Understanding of the accuracy of these volumes and ejection fractions (EF) by PET is clinically relevant, particularly in the sarcoid population where patients receive initial diagnostic CMR and then are followed by PET for inflammation. 89 patients undergoing cardiac sarcoidosis evaluation with both rest PET-CT and CMR within approximately 1 year were identified at Cleveland Clinic from 2011 to 2021. LV volumes and EF were collected. Linear regression and Bland–Altman analyses were performed. Mean PET-CT derived left ventricular ejection fraction (LVEF) was 46 ± 16% with mean LV end diastolic volume (LVEDV) of 127 ± 60 mL and mean LV end systolic volume (LVESV) of 75 ± 54 mL. Mean CMR-derived LVEF was 47 ± 15% with mean LVEDV of 189 ± 61 mL and mean LVESV of 106 ± 60 mL. Pearson correlation coefficient with standard measurements was 0.85 for EF, 0.80 for LVEDV, and 0.86 for LVESV. In our cohort, there is an excellent correlation of LVEF between PET-CT and CMR with a mean difference of 1.1% and a good correlation of volumes between these two imaging modalities. This has potential clinical implications when judging LVEF qualifications for medical and device therapies although future larger validation cohorts are warranted.
Association of cancer with the risk of developing hypertension
Authors: Nagasawa Hajime , Kaneko Hidehiro , Suzuki Yuta , Okada Akira , Fujiu Katsuhito , Takeda Norifumi , Morita Hiroyuki , Nishiyama Akira , Yano Yuichiro , Node Koichi , Viera Anthony J , Carey Robert M , Oparil Suzanne , Yasunaga Hideo , Touyz Rhian M , Komuro Issei
Published: June 2023

Background and aims

Although the importance of hypertension in patients with cancer is widely recognized, little is known about the risk of developing hypertension in patients with a history of cancer.

Methods and results

This retrospective observational cohort study analysed data from the JMDC Claims Database between 2005 and 2022, including 78 162 patients with a history of cancer and 3692 654 individuals without cancer. The primary endpoint was the incidence of hypertension.

During a mean follow-up period of 1208 ± 966 days, 311 197 participants developed hypertension. The incidence of hypertension was 364.6 [95% confidence interval (CI) 357.0–372.2] per 10 000 person-years among those with a history of cancer, and 247.2 (95% CI 246.3–248.1) per 10 000 person-years in those without cancer. Individuals with a history of cancer had an elevated risk of developing hypertension, according to multivariable Cox regression analyses [hazard ratio (HR) 1.17, 95% CI 1.15–1.20]. Both cancer patients requiring active antineoplastic therapy (HR 2.01, 95% CI 1.85–2.20), and those who did not require active antineoplastic therapy (HR 1.14, 95% CI 1.12–1.17) had an increased risk of hypertension. A multitude of sensitivity analyses confirmed the robustness of the relationship between cancer and incident hypertension. Patients with certain types of cancer were found to have a higher risk of developing hypertension than those without cancer, with varying risks dependent on the type of cancer.

Conclusion

Our analysis of a nationwide epidemiological database revealed that individuals with a history of cancer have a higher risk of developing hypertension, and this finding applies to both cancer patients who require active antineoplastic therapy and those who do not.
Partitioned Pricing and Collusion on Surcharges
Authors: Chen Zhiqi
Published: June 2023

Partitioned pricing is a pricing practice that divides the price of a product into a base price and one or more mandatory surcharges. This paper develops a theory of partitioned pricing using a duopoly model where the owner of each firm determines the surcharge, but delegates the setting of the base price to a manager. In equilibrium, both firms choose partitioned pricing over the conventional all-inclusive pricing. Moreover, partitioned pricing leads to higher full prices and larger profits than all-inclusive pricing. Most surprisingly, collusion on surcharges without any coordination on base prices is as profitable as collusion on all-inclusive prices.
Vine copula-based Bayesian classification for multivariate time series of electroencephalography eye states
Authors: Zhang Chunfang , Czado Claudia
Published: June 2023

Sometimes classification tasks have to be based on multivariate time series data collected for each class. In these situations the data for each class might exhibit non-stationary behaviour together with complex dependence structures. We propose a vine copula-based approach to capture these features in each class before applying a Bayesian classifier. Vine copulas have been very successful in modelling asymmetric tail dependence among variables and are coupled with non-stationary univariate time series to model the multivariate time series data for each class. We illustrate this classification approach using data from a neural activity experiment using electroencephalography, where we want to classify the eye state. The level of neural activity was collected over time for multiple locations on the scalp. Our approach is able to identify relevant locations and allows for a model-based interpretation of the data generating process. A cross-validation study with comparison to competitor classifiers for this data set shows good performance of the proposed classifier.
Species-specific responses of mammal activity to exurbanization in New Hampshire, USA
Authors: Poisson Mairi K P , Butler Andrew R , Tate Patrick , Bergeron Daniel H , Moll Remington J
Published: June 2023

Urbanization and habitat fragmentation can disrupt wildlife behavior and cause declines in biodiversity and ecosystem function. Most urban wildlife research has compared highly urbanized regions with rural areas. However, human development is also rapidly occurring in exurban areas, which consist of a matrix of lower-density housing and natural patches. Thus, although such “exurbanization” is intensifying, little research has examined how mammals respond to exurban development. To address this knowledge gap, we evaluated the activity of 12 species using 104 camera traps in exurban and rural areas across southeastern New Hampshire, USA, during summer 2021 and winter 2021–2. We quantified species’ activity levels (overall portion of daily activity) and patterns (variation of diel activity period) to test hypotheses regarding how species’ space requirements and nocturnality modulated their responses to exurban development. We found mixed support for our hypotheses. Two species with large space requirements (bobcats Lynx rufus and white-tailed deer Odocoileus virginianus) reduced activity levels in exurban areas, following hypothesized predictions, while other species (e.g., coyote Canis latrans) did not. As predicted, nocturnal species were less likely to shift activity patterns, but this varied across species and seasons. We also found evidence for a coupled predator–prey response among bobcats and lagomorphs in summer, with similarly altered activity in exurban areas. These results suggest that wildlife modify activity in response to exurban development with substantial species and season-specific variation within the mammal community, highlighting the complex ways wildlife adapt to urbanization and the potential consequences thereof for mammal communities.
Cooperation, Integration, and Assimilation: Abba Hillel Silver, Emanuel Neumann, the Lowdermilk Plan, and the Arab Question in the Forties
Authors: Segev Zohar
Published: June 2023

The growing power of the USA, of US Jewry, and of the US Zionist movement was a major factor that impacted Zionist policy during the 1940s. During this period, US Zionists sought to bring their influence to bear on the fundamental problems that the Zionist movement confronted during the war and thereafter. The Arab issue featured prominently in these efforts. While engaging with the questions of the relations between the Jews and the Arabs living in Palestine and with ways to make the Jewish state an integral part of the Middle East, the US Zionist leadership actively promoted the Lowdermilk Plan, which addressed the shortage of water in the region. US Zionist engagement with the Arab question signaled a fundamental change in the modes of operation of US Zionists and their desire to take an active and practical role in shaping the Jewish state and the Zionist movement. They were no longer content merely to provide material and political support to the Zionist movement and to the Jewish yishuv in Palestine.
High fidelity DNA strand-separation is the major specificity determinant in DNA methyltransferase CcrM’s catalytic mechanism
Authors: Konttinen Olivia , Carmody Jason , Kurnik Martin , Johnson Kenneth A , Reich Norbert
Published: June 2023

Strand-separation is emerging as a novel DNA recognition mechanism but the underlying mechanisms and quantitative contribution of strand-separation to fidelity remain obscure. The bacterial DNA adenine methyltransferase, CcrM, recognizes 5′GANTC′3 sequences through a DNA strand-separation mechanism with unusually high selectivity. To explore this novel recognition mechanism, we incorporated Pyrrolo-dC into cognate and noncognate DNA to monitor the kinetics of strand-separation and used tryptophan fluorescence to follow protein conformational changes. Both signals are biphasic and global fitting showed that the faster phase of DNA strand-separation was coincident with the protein conformational transition. Non-cognate sequences did not display strand-separation and methylation was reduced > 300-fold, providing evidence that strand-separation is a major determinant of selectivity. Analysis of an R350A mutant showed that the enzyme conformational step can occur without strand-separation, so the two events are uncoupled. A stabilizing role for the methyl-donor (SAM) is proposed; the cofactor interacts with a critical loop which is inserted between the DNA strands, thereby stabilizing the strand-separated conformation. The results presented here are broadly applicable to the study of other N6-adenine methyltransferases that contain the structural features implicated in strand-separation, which are found widely dispersed across many bacterial phyla, including human and animal pathogens, and some Eukaryotes.
The CSB chromatin remodeler regulates PARP1- and PARP2-mediated single-strand break repair at actively transcribed DNA regions
Authors: Bilkis Rabeya , Lake Robert J , Cooper Karen L , Tomkinson Alan , Fan Hua-Ying
Published: June 2023

Efficient repair of oxidized DNA is critical for genome-integrity maintenance. Cockayne syndrome protein B (CSB) is an ATP-dependent chromatin remodeler that collaborates with Poly(ADP-ribose) polymerase I (PARP1) in the repair of oxidative DNA lesions. How these proteins integrate during DNA repair remains largely unknown. Here, using chromatin co-fractionation studies, we demonstrate that PARP1 and PARP2 promote recruitment of CSB to oxidatively-damaged DNA. CSB, in turn, contributes to the recruitment of XRCC1, and histone PARylation factor 1 (HPF1), and promotes histone PARylation. Using alkaline comet assays to monitor DNA repair, we found that CSB regulates single-strand break repair (SSBR) mediated by PARP1 and PARP2. Strikingly, CSB’s function in SSBR is largely bypassed when transcription is inhibited, suggesting CSB-mediated SSBR occurs primarily at actively transcribed DNA regions. While PARP1 repairs SSBs at sites regardless of the transcription status, we found that PARP2 predominantly functions in actively transcribed DNA regions. Therefore, our study raises the hypothesis that SSBR is executed by different mechanisms based on the transcription status.
Mantle flow underneath the South China Sea revealed by seismic anisotropy
Authors: Kong Fansheng , Gao Rui , Gao Stephen S , Liu Kelly H , Ding Weiwei , Niu Xiongwei , Ruan Aiguo , Tan Pingchuan , Fan Jianke , Lu Shaoping , Tong Zhengyi , Cheng Liqun , Gong Wenfei , Zhao Yanghui , Li Jiabiao
Published: June 2023

It has long been established that plastic flow in the asthenosphere interacts constantly with the overlying lithosphere and plays a pivotal role in controlling the occurrence of geohazards such as earthquakes and volcanic eruptions. Unfortunately, accurately characterizing the direction and lateral extents of the mantle flow field is notoriously difficult, especially in oceanic areas where deployment of ocean bottom seismometers (OBSs) is expensive and thus rare. In this study, by applying shear wave splitting analyses to a dataset recorded by an OBS array that we deployed between mid-2019 and mid-2020 in the South China Sea (SCS), we show that the dominant mantle flow field has a NNW–SSE orientation, which can be attributed to mantle flow extruded from the Tibetan Plateau by the ongoing Indian–Eurasian collision. In addition, the results suggest that E–W oriented flow fields observed in South China and the Indochina Peninsula do not extend to the central SCS.
Genome-wide investigation of persistence with methotrexate treatment in early rheumatoid arthritis
Authors: Sysojev Anton Öberg , Saevarsdottir Saedis , Diaz-Gallo Lina-Marcela , Silberberg Gilad N , Alfredsson Lars , Klareskog Lars , Baecklund Eva , Björkman Lena , Kastbom Alf , Rantapää-Dahlqvist Solbritt , Turesson Carl , Jonsdottir Ingileif , Stefansson Kari , Frisell Thomas , Padyukov Leonid , Askling Johan , Westerlind Helga
Published: June 2023

Objectives

To investigate the influence of genetic factors on persistence with treatment of early RA with MTX monotherapy.

Methods

We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early-RA patients initiating MTX in DMARD monotherapy as their first-ever DMARD. The outcome, short- and long-term MTX treatment persistence, was defined as remaining on MTX at 1 and at 3 years, respectively, with no additional DMARDs added. As genetic predictors, we investigated individual SNPs, and then calculated a polygenic risk score (PRS) based on SNPs associated with RA risk. The SNP-based heritability of persistence was estimated overall and by RA serostatus.

Results

No individual SNP reached genome-wide significance (P < 5 × 10−8), either for persistence at 1 year or at 3 years. The RA PRS was not significantly associated with MTX treatment persistence at 1 year [relative risk (RR) = 0.98 (0.96–1.01)] or at 3 years [RR = 0.96 (0.93–1.00)]. The heritability of MTX treatment persistence was estimated to be 0.45 (0.15–0.75) at 1 year and 0.14 (0–0.40) at 3 years. The results in seropositive RA were comparable with those in the analysis of RA overall, while heritability estimates and PRS RRs were attenuated towards the null in seronegative RA.

Conclusion

Despite being the largest GWAS on an MTX treatment outcome to date, no genome-wide significant associations were detected. The modest heritability observed, coupled with the broad spread of suggestively associated loci, indicate that genetic influence is of polygenic nature. Nevertheless, MTX monotherapy persistence was lower in patients with a greater genetic disposition, per the PRS, towards RA.
Reliability of Respiratory System Compliance Calculation During Assisted Mechanical Ventilation: A Retrospective Study
Authors: Bastia Luca , Amendolagine Liliana , Pozzi Federico , Carenini Stefano , Cipolla Cristiana , Curto Francesco , Bellani Giacomo , Fumagalli Roberto , Chieregato Arturo
Published: June 2023

OBJECTIVES:

To compare respiratory system compliance (Crs) calculation during controlled mechanical ventilation (MV) and, subsequently, during assisted MV.

DESIGN:

This is a single-center, retrospective, observational study.

SETTING:

This study was conducted on patients admitted to Neuro-ICU of Niguarda Hospital (tertiary referral hospital).

PATIENTS:

We analyzed every patient greater than or equal to 18 years old having a Crs measurement in controlled and in assisted MV within 60 minutes. Plateau pressure (Pplat) was considered reliable if it was deemed visually stable for at least 2 seconds.

Interventions:

Inspiratory pause was incorporated to detect Pplat in controlled and assisted MV. Calculation of Crs and driving pressure were achieved.

MEASUREMENTS AND MAIN RESULTS:

A total of 101 patients were studied. An acceptable agreement was found (Bland-Altman plot bias –3.9, level of agreement upper 21.6, lower –29.6). Crs in assisted MV was 64.1 (52.6–79.3) and in controlled MV it was 61.2 (50–71.2) mL/cm H2
o (p = 0.006). No statistical difference was found in Crs (assisted vs controlled MV) when peak pressure was lower than Pplat nor when peak pressure was higher than Pplat.

CONCLUSIONS:

A Pplat visually stable for at least 2 seconds leads to reliable Crs calculation during assisted MV.
Durable control of metastases in an HLA-A2+ patient with refractory melanoma after low-dose radiotherapy in combination with MAGE-A4 T cell therapy: a case report
Authors: He Kewen , Hong David S. , Ke Danxia , Kebriaei Partow , Wang Tianjiao , Danesi Hassan , Bertolet Genevieve , Leuschner Carola , Puebla-Osorio Nahum , Voss Tiffany A. , Lin Quan , Norry Elliot , Fracasso Paula M. , Welsh James W.
Published: June 2023

There is no currently approved adoptive cellular therapy for solid tumors. Pre-clinical and clinical studies have demonstrated that low-dose radiotherapy (LDRT) can enhance intratumoral T cell infiltration and efficacy. This case report describes a 71-year-old female patient with rectal mucosal melanoma that had developed metastases to liver, lung, mediastinum, axillary nodes, and brain. After systemic therapies had failed, she enrolled in the radiation sub-study of our phase-I clinical trial exploring the safety and efficacy of afamitresgene autoleucel (afami-cel), genetically engineered T cells with a T cell receptor (TCR) targeting the MAGE-A4 tumor antigen in patients with advanced malignancies (NCT03132922). Prior to the infusion of afami-cel, she received concurrent lymphodepleting chemotherapy and LDRT at 5.6 Gy/4 fractions to the liver. Time to partial response was 10 weeks, and duration of overall response was 18.4 weeks. Although the patient progressed at 28 weeks, the disease was well controlled after high-dose radiotherapy to liver metastases and checkpoint inhibitors. As of the last follow-up, she remains alive over two years after LDRT and afami-cel therapy. This report suggests that afami-cel in combination with LDRT safely enhanced clinical benefit. This provides evidence for further exploring the benefit of LDRT in TCR-T cell therapy.
Review of the Etiology, Diagnosis, and Management of Left Ventricular Thrombus
Authors: Feldman Jared M. , Frishman William H. , Aronow Wilbert S.
Published: June 2023

The incidence of left ventricular (LV) thrombus following acute myocardial infarction has declined significantly due to recent advancements in reperfusion and antithrombotic therapies. The development of LV thrombus depends on Virchow’s triad: endothelial injury following myocardial infarction, blood stasis from LV dysfunction, and hypercoagulability. Diagnostic modalities for LV thrombus include transthoracic echocardiography and late gadolinium enhancement cardiac magnetic resonance imaging. Anticoagulation with direct oral anticoagulants or vitamin K antagonists for 3 months following initial diagnosis of LV thrombus remains the treatment of choice for LV thrombus. However, further evidence is needed to demonstrate the noninferiority of direct oral anticoagulants compared with vitamin K antagonists for the prevention of thromboembolic events.
Diversity, equity and inclusion in ophthalmology
Authors: Aguwa Ugochi T. , Williams Basil K. , Woreta Fasika A.
Published: June 2023

Purpose of review

Diversity, equity and inclusion (DEI) initiatives in ophthalmology have received increased attention in recent years. This review will highlight disparities, barriers to workforce diversity, as well as current and future efforts to improve DEI in ophthalmology.

Recent findings

Racial, ethnic, socioeconomic and sex disparities exist in vision health and across many ophthalmology subspecialties. The pervasive disparities result from factors such as a lack of access to eye care. In addition, ophthalmology is one of the least diverse specialties at the resident and faculty level. The lack of diversity has also been documented in ophthalmology clinical trials, wherein participant demographics do not reflect the diversity of the U.S. population.

Addressing social determinants of health including racism and discrimination is necessary to promote equity in vision health. Diversifying the workforce and expanding the representation of marginalized groups in clinical research are also paramount. Supporting existing programmes and creating new ones focusing on improving workforce diversity and reducing eye care disparities are essential to ensure equity in vision health for all Americans.