bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D PIC Simulations for Relativistic Jets with a Toroidal Magnetic Field
Authors: Nishikawa Kenichi , Meli Athina , Köhn Christoph , Duţan Ioana , Mizuno Yosuke , Kobzar Oleh , MacDonald Nicholas , Gómez José L. , Hirotani Kouichi 
Published: September 2023

AbstractParticle-in-Cell simulations can provide a possible answer to an important key issue for astrophysical plasma jets; namely on how a toroidal magnetic field affects the evolution of pair and electron-ion jets. We show that Weibel, mushroom, and kinetic Kelvin-Helmhotz instabilities excited at the linear stage, generate a quasi-steady x-component of the electric field which accelerates and decelerates electrons. We observe significant differences in the structure of the strong electromagnetic fields that are driven by the kinetic instabilities with the pair jet. We find that the two different jet compositions (e± and e– - i+) generate different instability modes respectively. Moreover, the magnetic field in the non-linear stage generated by different instabilities is dissipated and reorganized into new topologies. A 3D magnetic field topology depiction indicates possible reconnection sites in the non-linear stage where the particles are significantly accelerated by the dissipation of the magnetic field associated to a possible reconnection manifestation.
Satellite Observed Multisource Internal Tide Radiation and Interference in the Banda Sea
Authors: Zhang Peiwen , Xu Zhenhua , You Jia , Hao Zhanjiu , Yin Baoshu , Hou Yijun , Robertson Robin 
Published: September 2023

AbstractBoth the semidiurnal and diurnal internal tides in the Banda Sea were investigated using multi‐satellite altimeter data, through a combination of plane wave analysis technique and two‐dimensional band‐pass spatial filtering. The west and central Banda Sea are found to be dominated by semidiurnal internal tides, while the diurnal internal tides dominate the east. Multiple internal tidal sources were located at or nearby the Banda Arc, radiating significant internal tides inwards in complex interference patterns in the Banda Sea basin. The semidiurnal sources were situated on the northern and southern sides of the Banda Arc, emanating internal tides in opposite meridional directions. The semidiurnal tidal beams then experienced interference, shaping the heterogeneous energy fields in the west and central Banda Sea. The primary diurnal source was situated over the steep slope in the Aru Basin, with significant energy radiation westward and diffraction in the east Banda Sea. Based on the estimation of 27‐year coherent satellite results, the total energy flux of mode‐1 internal tides into the Banda Sea is about 4.82 GW, 58% contributed by semidiurnal tides and 42% by diurnal tides. This study represents the first observed mapping of the complex and inhomogeneous mode‐1 semidiurnal and diurnal internal tidal energy fields over the entire Banda Sea. Furthermore, this study enables further characterization of tidal mixing properties and improvement of model mixing parameterizations in the Indonesian seas.
Heterogeneous Strain Distribution in the Malawi (Nyasa) Rift, East Africa: Implications for Rifting in Magma‐Poor, Multi‐Segment Rift Systems
Authors: Wright Lachlan J. M. , Scholz Christopher A. , Muirhead James D. , Shillington Donna J. 
Published: September 2023

AbstractHalf‐graben basins bounded by border faults typify early‐stage continental rifts. Deciphering the role that intra‐rift faults play in rift basin development is challenging as patterns of early‐stage faulting are commonly overprinted by subsequent deformation; yet the characterization of these faults is crucial to understand the fundamental controls on their evolution, their contribution to rift opening, and to assess their seismic hazard. By integrating multiple offshore seismic reflection data sets with age‐dated drill core, late‐Quaternary and cumulative faulting patterns are characterized in the Central and South Basins of the Malawi (Nyasa) Rift, an active, early‐stage rift system. Almost all intra‐rift faults offset a late‐Quaternary lake lowstand surface, suggesting they are active and should be considered in hazard assessments. Fault throw profiles reveal sawtooth patterns indicating segmented slip histories. Observed extension on intra‐rift faults is approximately twice that predicted from hanging wall flexure of the border fault, suggesting that intra‐rift faults accommodate a proportion of the regional extension. Cumulative and late‐Quaternary throws on intra‐rift faults are correlated with throw measured on the border fault in the Central Basin, whereas an anticorrelation is observed in the South Basin. Viewed in a regional context, these differences do not relate solely to the proposed southward younging of the rift. Instead, it is inferred that the distribution of extension is also influenced by variations in lithospheric structure and crustal heterogeneities that are documented along the rift axis.
Magnitude, Trends, and Variability of the Global Ocean Carbon Sink From 1985 to 2018
Authors: DeVries Tim , Yamamoto Kana , Wanninkhof Rik , Gruber Nicolas , Hauck Judith , Müller Jens Daniel , Bopp Laurent , Carroll Dustin , Carter Brendan , Chau Thi‐Tuyet‐Trang , Doney Scott C. , Gehlen Marion , Gloege Lucas , Gregor Luke , Henson Stephanie , Kim Ji Hyun , Iida Yosuke , Ilyina Tatiana , Landschützer Peter , Le Quéré Corinne , Munro David , Nissen Cara , Patara Lavinia , Pérez Fiz F. , Resplandy Laure , Rodgers Keith B. , Schwinger Jörg , Séférian Roland , Sicardi Valentina , Terhaar Jens , Triñanes Joaquin , Tsujino Hiroyuki , Watson Andrew , Yasunaka Sayaka , Zeng Jiye 
Published: September 2023

AbstractThis contribution to the RECCAP2 (REgional Carbon Cycle Assessment and Processes) assessment analyzes the processes that determine the global ocean carbon sink, and its trends and variability over the period 1985–2018, using a combination of models and observation‐based products. The mean sea‐air CO2 flux from 1985 to 2018 is −1.6 ± 0.2 PgC yr−1 based on an ensemble of reconstructions of the history of sea surface pCO2 (pCO2 products). Models indicate that the dominant component of this flux is the net oceanic uptake of anthropogenic CO2, which is estimated at −2.1 ± 0.3 PgC yr−1 by an ensemble of ocean biogeochemical models, and −2.4 ± 0.1 PgC yr−1 by two ocean circulation inverse models. The ocean also degasses about 0.65 ± 0.3 PgC yr−1 of terrestrially derived CO2, but this process is not fully resolved by any of the models used here. From 2001 to 2018, the pCO2 products reconstruct a trend in the ocean carbon sink of −0.61 ± 0.12 PgC yr−1 decade−1, while biogeochemical models and inverse models diagnose an anthropogenic CO2‐driven trend of −0.34 ± 0.06 and −0.41 ± 0.03 PgC yr−1 decade−1, respectively. This implies a climate‐forced acceleration of the ocean carbon sink in recent decades, but there are still large uncertainties on the magnitude and cause of this trend. The interannual to decadal variability of the global carbon sink is mainly driven by climate variability, with the climate‐driven variability exceeding the CO2‐forced variability by 2–3 times. These results suggest that anthropogenic CO2 dominates the ocean CO2 sink, while climate‐driven variability is potentially large but highly uncertain and not consistently captured across different methods.
Numerical Investigation on the Height and Intensity Variations of Sporadic E Layers at Mid‐Latitude
Authors: Qiu Lihui , Yamazaki Yosuke , Yu Tao , Miyoshi Yasunobu , Zuo Xiaomin 
Published: September 2023

AbstractIn previous studies, various physical parameters, such as vertical wind shear null, vertical ion velocity null (IVN), and maximum gradient of vertical ion velocity, have been used as an indicator of Es layer height in light of the wind shear theory. Using a numerical Es layer model, we investigated which parameter represents the height of Es layer over Wuhan (114.4°E, 30.5°N) most precisely. The simulation results show that the height of Es layer above 110 km depends most strongly on the height of vertical IVN. However, below 110 km, the height of vertical IVN does not always agree with the height of Es layer. The analysis of simulation results suggests that the vertical gradient of the ratio of the ion‐neutral collision frequency (νi) to the ion gyrofrequency (ωi) affects the Es layer formation at lower altitudes (below 110 km). We also examined the effect of electric fields on the height and intensity of Es layers over Wuhan. It is found that eastward/upward electric fields can lift the Es layer height and reduce the Es layer intensity.
Indirect Observations of Electric Fields at Comet 67P
Authors: Moeslinger A. , Nilsson H. , Stenberg Wieser G. , Gunell H. , Goetz C. 
Published: September 2023

AbstractNo spacecraft visiting a comet has been equipped with instruments to directly measure the static electric field. However, the electric field can occasionally be estimated indirectly by observing its effects on the ion velocity distribution. We present such observations made by the Rosetta spacecraft on 19 April 2016, 35 km from the nucleus. At this time comet 67P was at a low outgassing rate and the plasma environment was relatively stable. The ion velocity distributions show the cometary ions on the first half of their gyration. We estimate the bulk drift velocity and the gyration speed from the distributions. By using the local measured magnetic field and assuming an E × B drift of the gyrocentre, we get an estimate for the average electric field driving this ion motion. We analyze a period of 13 hr, during which the plasma environment does not change drastically. We find that the average strength of the perpendicular electric field component is 0.21 mV/m. The direction of the electric field is mostly anti‐sunward. This is in agreement with previous results based on different methods.
Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy
Authors: Park Joon Seok , Gazzaniga Francesca S. , Kasper Dennis L. , Sharpe Arlene H. 
Published: September 2023

AbstractOur bodies are inhabited by trillions of microorganisms. The host immune system constantly interacts with the microbiota in barrier organs, including the intestines. Over decades, numerous studies have shown that our mucosal immune system is dynamically shaped by a variety of microbiota-derived signals. Elucidating the mediators of these interactions is an important step for understanding how the microbiota is linked to mucosal immune homeostasis and gut-associated diseases. Interestingly, the efficacy of cancer immunotherapies that manipulate costimulatory and coinhibitory pathways has been correlated with the gut microbiota. Moreover, adverse effects of these therapies in the gut are linked to dysregulation of the intestinal immune system. These findings suggest that costimulatory pathways in the immune system might serve as a bridge between the host immune system and the gut microbiota. Here, we review mechanisms by which commensal microorganisms signal immune cells and their potential impact on costimulation. We highlight how costimulatory pathways modulate the mucosal immune system through not only classical antigen-presenting cells but also innate lymphocytes, which are highly enriched in barrier organs. Finally, we discuss the adverse effects of immune checkpoint inhibitors in the gut and the possible relationship with the gut microbiota.
Zanubrutinib: past, present, and future
Authors: Tam Constantine S. , Muñoz Javier L. , Seymour John F. , Opat Stephen 
Published: September 2023

AbstractIn recent years, Bruton tyrosine kinase (BTK) inhibitors have provided significant advances in the treatment of patients with B-cell malignancies. Ibrutinib was the first BTK inhibitor to be approved, and it changed the standard-of-care treatment for diseases such as chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia, improving efficacy outcomes and safety compared to chemotherapy. In this article, we review the development of zanubrutinib, a next-generation BTK inhibitor, from molecular design to patient-related outcomes. We start this journey by providing insights into the discovery of BTK and the physiologic, genetic, and molecular characterization of patients lacking this kinase, together with the brief treatment landscape in the era of chemo-immunotherapies. Zanubrutinib was originally developed by applying a structure-activity strategy to enhance the specificity as well as enzymatic and pharmacokinetic properties. Preclinical studies confirmed greater specificity and better bioavailability of zanubrutinib compared with that of ibrutinib, which supported the initiation of clinical trials in humans. Preliminary clinical results indicated activity in B-cell malignancies together with an improved safety profile, in line with less off-target effects described in the preclinical studies. The clinical program of zanubrutinib has since expanded significantly, with ongoing studies in a wide range of hemato-oncological diseases and in combination with many other therapies. Zanubrutinib currently is approved for various B-cell malignancies in multiple countries. This story highlights the importance of multidisciplinary collaborative research, from bench to bedside, and provides an example of how the commitment to finding improved treatment options should always run parallel to patient care.
Treatment of older adults with FLT3-mutated AML: Emerging paradigms and the role of frontline FLT3 inhibitors
Authors: Short Nicholas J. , Nguyen Daniel , Ravandi Farhad 
Published: September 2023

AbstractFLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with FLT3 internal tandem duplication (ITD) mutations being associated with a more aggressive clinical course. While two large, randomized clinical trials have shown a survival benefit with the frontline use of an oral FLT3 inhibitor (midostaurin or quizartinib) in patients with FLT3-mutated AML, the role of FLT3 inhibitors in older adults with newly diagnosed FLT3-mutated AML remains unclear. A definitive improvement in survival has not been observed in intensively treated patients over 60 years of age receiving frontline FLT3 inhibitors. Furthermore, many patients with FLT3-mutated AML are unsuitable for intensive chemotherapy due to age and/or comorbidities, and this population represents a particular unmet need. For these older patients who are unfit for intensive approaches, azacitidine + venetoclax is a new standard of care and is used by many clinicians irrespective of FLT3 mutation status. However, FLT3-ITD mutations confer resistance to venetoclax and are a well-established mechanism of relapse to lower-intensity venetoclax-based regimens, leading to short durations of remission and poor survival. Preclinical and clinical data suggest synergy between FLT3 inhibitors and venetoclax, providing rationale for their combination. Novel strategies to safely incorporate FLT3 inhibitors into the standard hypomethylating agent + venetoclax backbone are now being explored in this older, less fit population with newly diagnosed FLT3-mutated AML, with encouraging early results. Herein, we discuss the frontline use of FLT3 inhibitors in older adults with FLT3-mutated AML, including the potential role of FLT3 inhibitors in combination with intensive chemotherapy and as part of novel, lower-intensity doublet and triplet regimens in this older population.
Adverse outcomes for chronic myeloid leukemia patients with splenomegaly and low in vivo kinase inhibition on imatinib
Authors: Kok Chung H. , Saunders Verity A. , Dang Phuong , Shanmuganathan Naranie , White Deborah , Branford Susan , Yeung David , Hughes Timothy P. 
Published: September 2023

AbstractVariability in the molecular response to frontline tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia may be partially driven by differences in the level of kinase inhibition induced. We measured in vivo BCR::ABL1 kinase inhibition (IVKI) in circulating mononuclear cells after 7 days of therapy. In 173 patients on imatinib 600 mg/day, 23% had low IVKI (<11% reduction in kinase activity from baseline); this was associated with higher rates of early molecular response (EMR) failure; lower rates of major molecular response (MMR), and MR4.5 by 36 months, compared to high IVKI patients. Low IVKI was more common (39%) in patients with large spleens (≥10 cm by palpation). Notably 55% of patients with large spleens and low IVKI experienced EMR failure whereas the EMR failure rate in patients with large spleens and high IVKI was only 12% (p = 0.014). Furthermore, patients with large spleen and low IVKI had a higher incidence of blast crisis, inferior MMR, MR4.5, and event-free survival compared to patients with large spleen and high IVKI and remaining patients. In nilotinib-treated patients (n = 73), only 4% had low IVKI. The combination of low IVKI and large spleen is associated with markedly inferior outcomes and interventions in this setting warrant further studies.
Identifying novel mechanisms of biallelic TP53 loss refines poor outcome for patients with multiple myeloma
Authors: Liu Enze , Sudha Parvathi , Becker Nathan , Jaouadi Oumaima , Suvannasankha Attaya , Lee Kelvin , Abonour Rafat , Abu Zaid Mohammad , Walker Brian A. 
Published: September 2023

AbstractBiallelic TP53 inactivation is the most important high-risk factor associated with poor survival in multiple myeloma. Classical biallelic TP53 inactivation has been defined as simultaneous mutation and copy number loss in most studies; however, numerous studies have demonstrated that other factors could lead to the inactivation of TP53. Here, we hypothesized that novel biallelic TP53 inactivated samples existed in the multiple myeloma population. A random forest regression model that exploited an expression signature of 16 differentially expressed genes between classical biallelic TP53 and TP53 wild-type samples was subsequently established and used to identify novel biallelic TP53 samples from monoallelic TP53 groups. The model reflected high accuracy and robust performance in newly diagnosed relapsed and refractory populations. Patient survival of classical and novel biallelic TP53 samples was consistently much worse than those with mono-allelic or wild-type TP53 status. We also demonstrated that some predicted biallelic TP53 samples simultaneously had copy number loss and aberrant splicing, resulting in overexpression of high-risk transcript variants, leading to biallelic inactivation. We discovered that splice site mutation and overexpression of the splicing factor MED18 were reasons for aberrant splicing. Taken together, our study unveiled the complex transcriptome of TP53, some of which might benefit future studies targeting abnormal TP53.
tgCRISPRi: efficient gene knock-down using truncated gRNAs and catalytically active Cas9
Authors: Auradkar Ankush , Guichard Annabel , Kaduwal Saluja , Sneider Marketta , Bier Ethan 
Published: September 2023

AbstractCRISPR-interference (CRISPRi), a highly effective method for silencing genes in mammalian cells, employs an enzymatically dead form of Cas9 (dCas9) complexed with one or more guide RNAs (gRNAs) with 20 nucleotides (nt) of complementarity to transcription initiation sites of target genes. Such gRNA/dCas9 complexes bind to DNA, impeding transcription of the targeted locus. Here, we present an alternative gene-suppression strategy using active Cas9 complexed with truncated gRNAs (tgRNAs). Cas9/tgRNA complexes bind to specific target sites without triggering DNA cleavage. When targeted near transcriptional start sites, these short 14–15 nts tgRNAs efficiently repress expression of several target genes throughout somatic tissues in Drosophila melanogaster without generating any detectable target site mutations. tgRNAs also can activate target gene expression when complexed with a Cas9-VPR fusion protein or modulate enhancer activity, and can be incorporated into a gene-drive, wherein a traditional gRNA sustains drive while a tgRNA inhibits target gene expression.
Modelling the dynamics of acute and chronic hepatitis B with optimal control
Authors: Khan Tahir , Rihan Fathalla A. , Ahmad Hijaz 
Published: September 2023

AbstractThis article examines hepatitis B dynamics under distinct infection phases and multiple transmissions. We formulate the epidemic problem based on the characteristics of the disease. It is shown that the epidemiological model is mathematically and biologically meaningful of its well-posedness (positivity, boundedness, and biologically feasible region). The reproductive number is then calculated to find the equilibria and the stability analysis of the epidemic model is performed. A backward bifurcation is also investigated in the proposed epidemic problem. With the help of two control measures (treatment and vaccination), we develop control strategies to minimize the infected population (acute and chronic). To solve the proposed control problem, we utilize Pontryagin’s Maximum Principle. Some simulations are conducted to illustrate the investigation of the analytical work and the effect of control analysis.
Measurement device-independent quantum key distribution with vector vortex modes under diverse weather conditions
Authors: Sekga Comfort , Mafu Mhlambululi 
Published: September 2023

AbstractMost quantum key distribution schemes exploiting orbital angular momentum-carrying optical beams are based on conventional set-ups, opening up the possibility of detector side-channel attacks. These optical beams also suffer from spatial aberrations due to atmospheric turbulence and unfavorable weather conditions. Consequently, we introduce a measurement device-independent quantum key distribution implemented with vector vortex modes. We study the transmission of vector vortex and scalar beams through a turbulent atmospheric link under diverse weather conditions such as rain or haze. We demonstrate that a maximum secure key transmission distance of 178 km can be achieved under clear conditions by utilizing the vector vortex beams, which have been mainly ignored in the literature. When raindrops have a diameter of 6 mm and fog particles have a radius of 0.5 $$\upmu$$
μ
m, the signals can reach 152 km and 160 km, respectively. Since these distances are comparable, this work sheds light into the feasibility of implementing measurement device-independent quantum key distribution using vector vortex modes under diverse weather conditions. Most significantly, this opens the door to practical secure quantum communications.
Synthesis of novel antibacterial nanocomposite CuO/Ag-modified zeolite for removal of MB dye
Authors: Yahya Nabil A. A. , Samir O. M. , Al-Ariki S. , Ahmed Amira A. M. , Swillam Mohamed A. 
Published: September 2023

AbstractNovel CuO/Ag nanocomposites added zeolite (CAZ) were successfully fabricated, and their effectiveness as an antibacterial on S. aureus and MB removal was evaluated. EDX, XRD, and FTIR confirm the presence of the elemental compositions of CAZ. Friable CuO nanorods (10–70 nm in diameter) existed on the surface of the zeolite. Pure zeolite had a higher band gap (5.433 eV) and lower MB removal efficiency than CAZ. The adsorption method by CAZ was more effective at removing MB than photodegradation. 0.10 CAZ had the highest removal effectiveness (~ 99%) and adsorption capacity (~ 70.4 mg g−1) of MB. The inhibitory zone diameter for 0.005 CAZ against S. aureus was 20 mm, while 0.01 CAZ had a diameter of 17 mm. Azithromycin, ceftriaxone, and erythromycin antibiotics demonstrated lower or no efficacy against S. aureus than CAZ. Significant antibacterial activities and wastewater treatment were achieved by CAZ. The combination of photodegradation and adsorption enhanced pollutant removal. It will be interesting to study further the optimal molar ratio for MB removal (0.10 CAZ) in future investigations.