bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the fibroblast growth factor pathway in molecular subtypes of castration‐resistant prostate cancer
Authors: Labrecque Mark P. , Brown Lisha G. , Coleman Ilsa M. , Nguyen Holly M. , Dalrymple Susan , Brennen W. Nathaniel , Isaacs John T. , Li Dapei , Lakely Bryce , DeLucia Diana C. , Lee John K. , Schweizer Michael T. , Lin Daniel W. , Corey Eva , Nelson Peter S. , Morrissey Colm 
Published: October 2023

AbstractBackgroundAndrogen receptor (AR) pathway inhibition remains the cornerstone for prostate cancer therapies. However, castration‐resistant prostate cancer (CRPC) tumors can resist AR signaling inhibitors through AR amplification and AR splice variants in AR‐positive CRPC (ARPC), and conversion to AR‐null phenotypes, such as double‐negative prostate cancer (DNPC) and small cell or neuroendocrine prostate cancer (SCNPC). We have shown previously that DNPC can bypass AR‐dependence through fibroblast growth factor receptor (FGFR) signaling. However, the role of the FGFR pathway in other CRPC phenotypes has not been elucidated.MethodsRNA‐Seq analysis was conducted on patient metastases, LuCaP patient‐derived xenograft (PDX) models, and CRPC cell lines. Cell lines (C4‐2B, VCaP, and 22Rv1) and ex vivo LuCaP PDX tumor cells were treated with enzalutamide (ENZA) and FGFR inhibitors (FGFRi) alone or in combination and sensitivity was determined using cell viability assays. In vivo efficacy of FGFRi in ARPC, DNPC, and SCNPC were evaluated using PDX models.ResultsRNA‐Seq analysis of FGFR signaling in metastatic specimens, LuCaP PDX models, and CRPC cell lines revealed significant FGF pathway activation in AR‐low PC (ARLPC), DNPC, and SCNPC tumors. In vitro/ex vivo analysis of erdafitinib and CH5183284 demonstrated robust and moderate growth suppression of ARPC, respectively. In vivo studies using four ARPC PDX models showed that combination ENZA and CH5183284 significantly suppressed tumor growth. Additional in vivo studies using four ARPC PDX models revealed that erdafitinib monotherapy was as effective as ENZA in suppressing tumor growth, and there was limited combination benefit. Furthermore, two of three DNPC models and two of four SCNPC models responded to CH5183284 monotherapy, suggesting FGFRi responses were model dependent. RNA‐Seq and gene set enrichment analysis of end‐of‐study ARPC tumors treated with FGFRi displayed decreased expression of E2F and MYC target genes and suppressed G2M checkpoint genes, whereas end‐of‐study SCNPC tumors had heterogeneous transcriptional responses.ConclusionsAlthough FGFRi treatments suppressed tumor growth across CRPC phenotypes, our analyses did not identify a single pathway or biomarker that would identify tumor response to FGFRi. This is very likely due to the array of FGFR1–4 expression and tumor phenotypes present in CRPC. Nevertheless, our data nominate the FGFR pathway as a clinically actionable target that promotes tumor growth in diverse phenotypes of treatment‐refractory metastatic CRPC.
Novel sliding‐mode control for a class of second‐order systems with mismatched disturbances
Authors: Fu Baozeng , Che Weiwei , Liu Yongchao , Wang Qingzhi , Yu Haisheng 
Published: October 2023

AbstractThis article investigates a novel sliding‐mode control (SMC) approach for a class of second‐order nonlinear systems subject to mismatched disturbances. To solve this problem, a novel sliding surface is designed based on the disturbance estimation of the nonlinear disturbance observer (DOB). By designing a novel time‐varying switching gain, a DOB‐based improved SMC law is constructed to compensate the influence of mismatched disturbances on the system output and make the system output converge asymptotically to zero. The novel SMC scheme owns two advantages. One is that the switching gain is an exponential decay function varying synchronously with the disturbance estimation error, which substantially alleviates the chattering problem. The other one is that a new function is defined as the switching gain coefficient based on the disturbance estimation, which helps the proposed approach to maintain the nominal control performance of the system, that is, the novel SMC law degrades to the baseline SMC law in the absence of disturbances. A numerical simulation example verifies the effectiveness and superiority of the developed approach by comparisons.
Design and implementation of resource‐aware robust event‐based integral sliding mode controller for a networked wheeled mobile robot
Authors: Nath Krishanu , Bera Manas Kumar 
Published: October 2023

AbstractThis work discusses the design and implementation of a robust control strategy based on integral sliding mode (ISM) for tracking a reference trajectory by a nonholonomic wheeled mobile robot (WMR). A state feedback control law using dynamic feedback linearization is adopted to design the controller for the unperturbed dynamics of the WMR. To nullify the effects of perturbations in the WMR and to retain the performance of the nominal controller, the ISM control scheme is introduced, which uses discontinuous control to guarantee the robustness of the closed‐loop system. To relax the frequent use of the communication network due to the continuous exchange of the sensor measurements, the control law is redesigned using event‐based sampled data information. The control signal is updated in an aperiodic manner by designing a novel triggering rule where the triggering occurs only when either of the two sampling errors violates a predefined threshold condition. This design approach gives a balanced solution for a networked WMR regarding network usage and control performance. Finally, a simulation study with comparative analysis and hardware‐in‐loop testing of the proposed controller is performed on a mobile robot system to establish the feasibility of the theoretical results.
Bone‐Targeted Biomimetic Nanogels Re‐Establish Osteoblast/Osteoclast Balance to Treat Postmenopausal Osteoporosis
Authors: Cui Yongzhi , Lv Bin , Li Zhongying , Ma Chunming , Gui Zhengwei , Geng Yongtao , Liu Guohui , Sang Linchao , Xu Chen , Min Qi , Kong Li , Zhang Zhiping , Liu Yang , Qi Xiangbei , Fu Dehao 
Published: October 2023

AbstractInsufficient bone formation and excessive bone resorption caused by estrogen deficiency are the major factors resulting in the incidence of postmenopausal osteoporosis (PMOP). The existing drugs usually fail to re‐establish the osteoblast/osteoclast balance from both sides and generate side‐effects owing to the lack of bone‐targeting ability. Here, engineered cell‐membrane‐coated nanogels PNG@mR&C capable of scavenging receptor activator of nuclear factor‐κB ligand (RANKL) and responsively releasing therapeutic PTH 1–34 in the bone microenvironment are prepared from RANK and CXCR4 overexpressed bone mesenchymal stem cell (BMSC) membrane‐coated chitosan biopolymers. The CXCR4 on the coated‐membranes confer bone‐targeting ability, and abundant RANK effectively absorb RANKL to inhibit osteoclastogenesis. Meanwhile, the release of PTH 1–34 triggered by osteoclast‐mediated acid microenvironment promote osteogenesis. In addition, the dose and frequency are greatly reduced due to the smart release property, prolonged circulation time, and bone‐specific accumulation. Thus, PNG@mR&C exhibits satisfactory therapeutic effects in the ovariectomized (OVX) mouse model. This study provides a new paradigm re‐establishing the bone metabolic homeostasis from multitargets and shows great promise for the treatment of PMOP.
Implications of structural design on the effectiveness of active vibration control of floor structures
Authors: Hudson E J. , Reynolds P. 
Published: October 2023

SUMMARYActive vibration control has shown great potential for reducing the response of floor structures and has the potential to realise significant material savings in slender designs through incorporation from the conceptual stage. However, different structural designs result in different modal properties, and these can significantly affect the effectiveness of an active vibration control implementation.This paper investigates the implications of these different structural designs. Two floor structures with known vibration serviceability issues are considered; both of these are fairly typical designs. Active control is then simulated on each floor in order to improve the response of the structure.A multipedestrian walking force model is developed and used to generate the response of each structure. This loading model is calibrated and verified using experimentally acquired data on the structures considered.It was found that the effectiveness of the control was localised to each structural panel, and therefore the structural design that yielded larger panels required fewer actuators to reduce the response over the entire structure. Copyright © 2013 John Wiley & Sons, Ltd.
Assessing urban transformational strategies through innovative farming practices in the Johannesburg city center
Authors: Ngie Adeline , Sithole Nobukhosi 
Published: October 2023

AbstractThe Johannesburg metropolitan city, which is the largest city in South Africa, like others in most emerging or developing economies, is plagued by numerous challenges among which is food insecurity. The numerous skyscrapers to maximize land space over the years without adequate maintenance pose as deteriorated sites. Technological advancement has then improved these sites and provided not only regenerated buildings and spaces but also solutions to food insecurity for the inhabitants through transformational strategies from the local government. These strategies have promoted urban agriculture and introduced innovative farming measures such as rooftop gardening and hydroponic farming. These measures have been geared toward attaining sustainable environmental goals for land and water optimization within limited land spaces in the inner‐city center. This study assessed the state of these measures toward attaining the environmental goals by engaging stakeholders where open‐ended interviews were used to obtain experiences. Results showed that transformational strategies have not only improved household food security and created income‐generating opportunities but also regenerated the infrastructure of the city center. However, numerous challenges are threatening the complete realization, which are soil and water flow availability to the rooftop gardens. The situation is better with hydroponics though with its own hurdles, including the need for consistent energy supplies, input costs, and technological challenges. Overall, hydroponics presents a more promising solution to attaining land and water resource use efficiency goals with proper governance and policy support.
Comparisons of Absolute Gravimeters as a Key Component of the International Terrestrial Gravity Reference Frame (ITGRF) Shown on the Example of the WET-CAG2021 at Wettzell, Germany
Authors: Wziontek Hartmut , Falk Reinhard , Pálinkáš Vojtech , Engfeldt Andreas , Glässel Julian , Hellerschmied Andreas , Iacovone Domenico , Kostelecky Jakub , Reich Marvin , Timmen Ludger , Ullrich Christian , Valluzzi Alessandro , Zehetmaier Barbara 
Published: October 2023

AbstractComparisons of absolute gravimeters are essential to guarantee their traceability to the International System of Units (SI) and their compatibility and will be a key component of the upcoming International Terrestrial Gravity Reference Frame (ITGRF) of IAG.The results of the regional comparison of absolute gravimeters WET-CAG2021 hosted at the Geodetic Observatory Wettzell, Germany, in autumn 2021 are presented. Seven FG5/X absolute gravimeters and—for the first time—two commercial AQG absolute quantum gravimeters took part. Temporal gravity variations during the comparison period of 12 weeks were monitored with the superconducting gravimeter GWR OSG-030. The equivalence of each absolute gravimeter is evaluated against a common reference level derived from the measurements during this comparison period. Although the comparison is outside the scope of CIPM MRA it is linked to the EURAMET.M.G-K3 2018 at the same site and the CM.G-K2.2017 in Beijing, China, which ensures the traceability.
The Software Heritage Open Science Ecosystem
Authors: Cosmo Roberto Di , Zacchiroli Stefano 
Published: October 2023

AbstractSoftware Heritage is the largest public archive of software source code and associated development history, as captured by modern version control systems. As of July 2023, it has archived more than 16 billion unique source code files coming from more than 250 million collaborative development projects. In this chapter, we describe the Software Heritage ecosystem, focusing on research and open science use cases.On the one hand, Software Heritage supports empirical research on software by materializing in a single Merkle direct acyclic graph the development history of public code. This giant graph of source code artifacts (files, directories, and commits) can be used –and has been used– to study repository forks, open source contributors, vulnerability propagation, software provenance tracking, source code indexing, and more.On the other hand, Software Heritage ensures availability and guarantees integrity of the source code of software artifacts used in any field that relies on software to conduct experiments, contributing to making research reproducible. The source code used in scientific experiments can be archived –e.g., via integration with open-access repositories – referenced using persistent identifiers that allow downstream integrity checks and linked to/from other scholarly digital artifacts.
Neff constraints on light mediators coupled to neutrinos: the dilution-resistant effect
Authors: Li Shao-Ping , Xu Xun-Jie 
Published: October 2023

Abstract
We investigate the impact of new light particles, carrying significant energy in the early universe after neutrino decoupling, on the cosmological effective relativistic neutrino species, Neff. If the light particles are produced from decoupled neutrinos, Neff is predominantly modified through the dilution-resistant effect. This effect arises because the energy stored in the mass of new particles is less diluted than the photon and neutrino energy as the universe expands. Our study comprehensively explores this effect, deriving Neff constraints on the couplings of light mediators with neutrinos, encompassing both scalar and vector mediators. We find that the dilution-resistant effect can increase Neff by 0.118 and 0.242 for scalar and vector mediators, respectively. These values can be readily reached by forthcoming CMB experiments. Upon reaching these levels, future Neff constraints on the couplings will be improved by many orders of magnitude.
The cosmological constant is probably still zero
Authors: Liu Yang , Padilla Antonio , Pedro Francisco G. 
Published: October 2023

Abstract
We consider a wide class of four-dimensional effective field theories in which gravity is coupled to multiple four-forms and their dual scalar fields, with membrane sources charged under the corresponding three-form potentials. Four-form flux, quantised in units of the membrane charges, generically generates a landscape of vacua with a range of values for the cosmological constant that is scanned through membrane nucleation. We list various ways in which the landscape can be made sufficiently dense to be compatible with observations of the current vacuum without running into the empty universe problem. Further, we establish the general criteria required to ensure the absolute stability of the Minkowski vacuum under membrane nucleation and the longevity of those vacua that are parametrically close by. This selects the current vacuum on probabilistic grounds and can even be applied in the classic model of Bousso and Polchinski, albeit with some mild violation of the membrane weak gravity conjecture. We present other models where the membrane weak gravity conjecture is not violated but where the same probabilistic methods can be used to tackle the cosmological constant problem.
Behavioral responses of free-flying Drosophila melanogaster to shiny, reflecting surfaces
Authors: Mathejczyk Thomas F. , Babo Édouard J. , Schönlein Erik , Grinda Nikolai V. , Greiner Andreas , Okrožnik Nina , Belušič Gregor , Wernet Mathias F. 
Published: October 2023

AbstractActive locomotion plays an important role in the life of many animals, permitting them to explore the environment, find vital resources, and escape predators. Most insect species rely on a combination of visual cues such as celestial bodies, landmarks, or linearly polarized light to navigate or orient themselves in their surroundings. In nature, linearly polarized light can arise either from atmospheric scattering or from reflections off shiny non-metallic surfaces like water. Multiple reports have described different behavioral responses of various insects to such shiny surfaces. Our goal was to test whether free-flying Drosophila melanogaster, a molecular genetic model organism and behavioral generalist, also manifests specific behavioral responses when confronted with such polarized reflections. Fruit flies were placed in a custom-built arena with controlled environmental parameters (temperature, humidity, and light intensity). Flight detections and landings were quantified for three different stimuli: a diffusely reflecting matt plate, a small patch of shiny acetate film, and real water. We compared hydrated and dehydrated fly populations, since the state of hydration may change the motivation of flies to seek or avoid water. Our analysis reveals for the first time that flying fruit flies indeed use vision to avoid flying over shiny surfaces.
Surgical treatment and overall survival in patients with right-sided obstructing colon cancer—a nationwide retrospective cohort study
Authors: Boeding Jeske R. E. , Elferink Marloes A. G. , Tanis Pieter J. , de Wilt Johannes H. W. , Gobardhan Paul D. , Verhoef Cornelis , Schreinemakers Jennifer M. J. 
Published: October 2023

Abstract
Purpose
The aim of this study was to compare baseline characteristics, 90-day mortality and overall survival (OS) between patients with obstructing and non-obstructing right-sided colon cancer at a national level.

Methods
All patients who underwent resection for right-sided colon cancer between January 2015 and December 2016 were selected from the Netherlands Cancer Registry and stratified for obstruction. Primary outcome was 5-year OS after excluding 90-day mortality as assessed by the Kaplan-Meier and multivariable Cox regression analysis.

Results
A total of 525 patients (7%) with obstructing and 6891 patients (93%) with non-obstructing right-sided colon cancer were included. Patients with right-sided obstructing colon cancer (OCC) were older and had more often transverse tumour location, and the pathological T and N stage was more advanced than in those without obstruction (p < 0.001). The 90-day mortality in patients with right-sided OCC was higher compared to that in patients with non-obstructing colon cancer: 10% versus 3%, respectively (p < 0.001). The 5-year OS of those surviving 90 days postoperatively was 42% in patients with OCC versus 73% in patients with non-obstructing colon cancer, respectively (p < 0.001). Worse 5-year OS was found in patients with right-sided OCC for all stages. Obstruction was an independent risk factor for decreased OS in right-sided colon cancer (HR 1.79, 95% CI 1.57–2.03).

Conclusion
In addition to increased risk of postoperative mortality, a stage-independent worse 5-year OS after excluding 90-day mortality was found in patients with right-sided OCC compared to patients without obstruction.
Mitophagy for cardioprotection
Authors: Titus Allen Sam , Sung Eun-Ah , Zablocki Daniela , Sadoshima Junichi 
Published: October 2023

AbstractMitochondrial function is maintained by several strictly coordinated mechanisms, collectively termed mitochondrial quality control mechanisms, including fusion and fission, degradation, and biogenesis. As the primary source of energy in cardiomyocytes, mitochondria are the central organelle for maintaining cardiac function. Since adult cardiomyocytes in humans rarely divide, the number of dysfunctional mitochondria cannot easily be diluted through cell division. Thus, efficient degradation of dysfunctional mitochondria is crucial to maintaining cellular function. Mitophagy, a mitochondria specific form of autophagy, is a major mechanism by which damaged or unnecessary mitochondria are targeted and eliminated. Mitophagy is active in cardiomyocytes at baseline and in response to stress, and plays an essential role in maintaining the quality of mitochondria in cardiomyocytes. Mitophagy is mediated through multiple mechanisms in the heart, and each of these mechanisms can partially compensate for the loss of another mechanism. However, insufficient levels of mitophagy eventually lead to mitochondrial dysfunction and the development of heart failure. In this review, we discuss the molecular mechanisms of mitophagy in the heart and the role of mitophagy in cardiac pathophysiology, with the focus on recent findings in the field.
On Triple Lines and Cubic Curves: The Orchard Problem Revisited
Authors: Elekes György , Szabó Endre 
Published: October 2023

AbstractPlanar point sets with many triple lines (which contain at least three distinct points of the set) have been studied for 180 years, started with Jackson and followed by Sylvester. Green and Tao (Discret Comput Geom 50(2):409–468, 2013) have shown that the maximum possible number of triple lines for an n-element set is $$\lfloor n\hspace{0.33325pt}(n - 3)/6\rfloor + 1$$

⌊
n

(
n
-
3
)
/
6
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+
1

. Here we address the related problem of describing the structure of the asymptotically near-optimal configurations, i.e., of those for which the number of straight lines which go through three or more points has a quadratic (i.e., best possible) order of magnitude. We pose the problem whether such point sets must always be related to cubic curves. To support this conjecture we settle various special cases; some of them are also related to the four-in-a-line problem of Erdős.
Multi-objective reward generalization: improving performance of Deep Reinforcement Learning for applications in single-asset trading
Authors: Cornalba Federico , Disselkamp Constantin , Scassola Davide , Helf Christopher 
Published: October 2023

AbstractWe investigate the potential of Multi-Objective, Deep Reinforcement Learning for stock and cryptocurrency single-asset trading: in particular, we consider a Multi-Objective algorithm which generalizes the reward functions and discount factor (i.e., these components are not specified a priori, but incorporated in the learning process). Firstly, using several important assets (BTCUSD, ETHUSDT, XRPUSDT, AAPL, SPY, NIFTY50), we verify the reward generalization property of the proposed Multi-Objective algorithm, and provide preliminary statistical evidence showing increased predictive stability over the corresponding Single-Objective strategy. Secondly, we show that the Multi-Objective algorithm has a clear edge over the corresponding Single-Objective strategy when the reward mechanism is sparse (i.e., when non-null feedback is infrequent over time). Finally, we discuss the generalization properties with respect to the discount factor. The entirety of our code is provided in open-source format.