bluuebunny/crossref_metadata_2025 huggingface dataset:
The symbol and alphabet of two-loop NMHV amplitudes from $$ \overline{Q} $$ equations
Authors: He Song , Li Zhenjie , Zhang Chi
Published: March 2021

Abstract

We study the symbol and the alphabet for two-loop NMHV amplitudes in planar $$ \mathcal{N} $$
N
= 4 super-Yang-Mills from the $$ \overline{Q} $$

Q
¯

equations, which provide a first-principle method for computing multi-loop amplitudes. Starting from one-loop N2MHV ratio functions, we explain in detail how to use $$ \overline{Q} $$

Q
¯

equations to obtain the total differential of two-loop n-point NMHV amplitudes, whose symbol contains letters that are algebraic functions of kinematics for n ≥ 8. We present explicit formula with nice patterns for the part of the symbol involving algebraic letters for all multiplicities, and we find 17 − 2m multiplicative-independent letters for a given square root of Gram determinant, with 0 ≤ m ≤ 4 depending on the number of particles involved in the square root. We also observe that these algebraic letters can be found as poles of one-loop four-mass leading singularities with MHV or NMHV trees. As a byproduct of our algebraic results, we find a large class of components of two-loop NMHV, which can be written as differences of two double-pentagon integrals, particularly simple and free of square roots. As an example, we present the complete symbol for n = 9 whose alphabet contains 59 × 9 rational letters, in addition to the 11 × 9 independent algebraic ones. We also give all-loop NMHV last-entry conditions for all multiplicities.
Winding uplifts and the challenges of weak and strong SUSY breaking in AdS
Authors: Hebecker Arthur , Leonhardt Sascha
Published: March 2021

Abstract

We discuss the problem of metastable SUSY breaking in the landscape. While this is clearly crucial for the various de Sitter proposals, it is also interesting to consider the SUSY breaking challenge in the AdS context. For example, it could be that a stronger form of the non-SUSY AdS conjecture holds: it would forbid even metastable non-SUSY AdS in cases where the SUSY-breaking scale is parametrically above/below the AdS scale. At the technical level, the present paper proposes to break SUSY using the multi-cosine-shaped axion potentials which arise if a long winding trajectory of a ‘complex-structure axion’ appears in the large-complex-structure limit of a Calabi-Yau orientifold. This has been studied in the context of ‘Winding Inflation’, but the potential for SUSY breaking has not been fully explored. We discuss the application to uplifting LVS vacua, point out the challenges which one faces in the KKLT context, and consider the possibility of violating the non-SUSY AdS conjecture in the type-IIA setting of DGKT.
Recursion relations for scattering amplitudes with massive particles
Authors: Ballav Sourav , Manna Arkajyoti
Published: March 2021

Abstract

We use the recently developed massive spinor-helicity formalism [1] of Arkani-Hamed et al. to study a new class of recursion relations for tree-level amplitudes in gauge theories. These relations are based on a combined complex deformation of massless as well as massive external momenta. We use these relations to study tree-level amplitudes in scalar QCD as well as amplitudes involving massive vector bosons in the Higgsed phase of Yang-Mills theory. We prove the validity of our proposal by showing that in the limit of infinite momenta of two of the external particles, the amplitude once again is controlled by an enhanced Spin-Lorentz symmetry paralleling the proof of BCFW shift for massless gauge theories. Simple examples illustrate that the proposed shift may lead to an efficient computation of tree-level amplitudes.
Particle production from oscillating scalar field and consistency of Boltzmann equation
Authors: Moroi Takeo , Yin Wen
Published: March 2021

Abstract

Boltzmann equation plays important roles in particle cosmology in studying the evolution of distribution functions (also called as occupation numbers) of various particles. For the case of the decay of a scalar condensation ϕ into a pair of scalar particles (called χ), we point out that the system may not be well described by the Boltzmann equation when the occupation number of χ becomes large even in the so-called narrow resonance regime. We study the particle production including the possible enhancement due to a large occupation number of the final state particle, known as the stimulated emission or the parametric resonance. Based on the quantum field theory (QFT), we derive a set of equations which directly govern the evolution of the distribution function of χ. Comparing the results of the QFT calculation and those from the Boltzmann equation, we find non-agreements in some cases. In particular, in the expanding Universe, the occupation number of χ based on the QFT may differ by many orders of magnitude from that from the Boltzmann equation. We also discuss a possible relation between the evolution equations based on the QFT and the Boltzmann equation.
The role of heme oxygenase-1 in hematopoietic system and its microenvironment
Authors: Szade Agata , Szade Krzysztof , Mahdi Mahdi , Józkowicz Alicja
Published: March 2021

Hematopoietic system transports all necessary nutrients to the whole organism and provides the immunological protection. Blood cells have high turnover, therefore, this system must be dynamically controlled and must have broad regeneration potential. In this review, we summarize how this complex system is regulated by the heme oxygenase-1 (HO-1)—an enzyme, which degrades heme to biliverdin, ferrous ion and carbon monoxide. First, we discuss how HO-1 influences hematopoietic stem cells (HSC) self-renewal, aging and differentiation. We also describe a critical role of HO-1 in endothelial cells and mesenchymal stromal cells that constitute the specialized bone marrow niche of HSC. We further discuss the molecular and cellular mechanisms by which HO-1 modulates innate and adaptive immune responses. Finally, we highlight how modulation of HO-1 activity regulates the mobilization of bone marrow hematopoietic cells to peripheral blood. We critically discuss the issue of metalloporphyrins, commonly used pharmacological modulators of HO-1 activity, and raise the issue of their important HO-1-independent activities.
Correction to: Special Kähler structures, cubic differentials and hyperbolic metrics
Authors: Haydys Andriy , Xu Bin
Published: March 2021

A correction to this paper has been published: https://doi.org/10.1007/s00029-021-00643-4
Estimating ambiguity fixed satellite orbit, integer clock and daily bias products for GPS L1/L2, L1/L5 and Galileo E1/E5a, E1/E5b signals
Authors: Duan Bingbing , Hugentobler Urs , Selmke Inga , Wang Ningbo
Published: March 2021

Ambiguity resolution of a single receiver is becoming more and more popular for precise GNSS (Global Navigation Satellite System) applications. To serve such an approach, dedicated satellite orbit, clock and bias products are needed. However, we need to be sure whether products based on specific frequencies and signals can be used when processing measurements of other frequencies and signals. For instance, for Galileo E5a frequency, some receivers track only the pilot signal (C5Q) while some track only the pilot-data signal (C5X). We cannot compute the differences between C5Q and C5X directly since these two signals are not tracked concurrently by any common receiver. As code measurements contribute equally as phase in the Melbourne-Wuebbena (MelWub) linear combination it is important to investigate whether C5Q and C5X can be mixed in a network to compute a common satellite MelWub bias product. By forming two network clusters tracking Q and X signals, respectively, we confirm that GPS C5Q and C5X signals cannot be mixed together. Because the bias differences between GPS C5Q and C5X can be more than half of one wide-lane cycle. Whereas, mixing of C5Q and C5X signals for Galileo satellites is possible. The RMS of satellite MelWub bias differences between Q and X cluster is about 0.01 wide-lane cycles for both E1/E5a and E1/E5b frequencies. Furthermore, we develop procedures to compute satellite integer clock and narrow-lane bias products using individual dual-frequency types. Same as the finding from previous studies, GPS satellite clock differences between L1/L2 and L1/L5 estimates exist and show a periodical behavior, with a peak-to-peak amplitude of 0.7 ns after removing the daily mean difference of each satellite. For Galileo satellites, the maximum clock difference between E1/E5a and E1/E5b estimates after removing the mean value is 0.04 ns and the mean RMS of differences is 0.015 ns. This is at the same level as the noise of the carrier phase measurement in the ionosphere-free linear combination. Finally, we introduce all the estimated GPS and Galileo satellite products into PPP-AR (precise point positioning, ambiguity resolution) and Sentinel-3A satellite orbit determination. Ambiguity fixed solutions show clear improvement over float solutions. The repeatability of five ground-station coordinates show an improvement of more than 30% in the east direction when using both GPS and Galileo products. The Sentinel-3A satellite tracks only GPS L1/L2 measurements. The standard deviation (STD) of satellite laser ranging (SLR) residuals is reduced by about 10% when fixing ambiguity parameters to integer values.
Influence of fruit logistics on fresh-cut pineapple (Ananas comosus [L.] Merr.) volatiles assessed by HS-SPME–GC–MS analysis
Authors: Steingass Christof B. , Dickreuter Jennifer , Kuebler Sabine , Schweiggert Ralf M. , Carle Reinhold
Published: March 2021

Green-ripe pineapples are shipped overseas by sea freight, while those picked at full maturity need to be transported by airfreight over the same large distance. In this study, fresh-cut pineapple cubes were assessed two, five, and eight days after processing from green-ripe pineapples after mimicked sea freigh (SF) and fully ripe air-freighted (AF) pineapples. The sea-freighted samples displayed elevated titratable acidity (TA), thus resulting in smaller ratios of total soluble solids and TA compared to the AF pineapples. Differences in the carotenoid levels of the two fresh-cut categories were found to be insignificant. By contrast, hierarchical cluster analysis (HCA) and principal component analysis (PCA) calculated on the basis of the volatiles analysed by headspace solid-phase microextraction–gas chromatography–mass spectrometry (HS-SPME–GC–MS) permitted to distinguish all six individual sample types and to segregate them into two major clusters (SF and AF). The effect of storage on the volatiles was further evaluated by partial least squares (PLS) regression. Substantial chemical markers to differentiate the individual samples and to describe the effect of storage were deduced from the PCA and PLS regression, respectively. In general, fresh-cut products obtained from fully ripe AF fruit displayed higher concentrations of volatiles, in particular, increased concentrations of diverse methyl esters. With progressing storage duration, the concentrations of ethanol and diverse ethyl esters increased. Moreover, products from AF pineapples displayed lower microbial counts compared to those from SF fruit.
Inhibition of STAT3 augments antitumor efficacy of anti-CTLA-4 treatment against prostate cancer
Authors: Witt Kristina , Evans-Axelsson Susan , Lundqvist Andreas , Johansson Martin , Bjartell Anders , Hellsten Rebecka
Published: March 2021

There is an urgent need for new treatment options in metastatic drug-resistant prostate cancer. Combining immunotherapy with other targeted therapies may be an effective strategy for advanced prostate cancer. In the present study, we sought to investigate to enhance the efficacy of anti-CTLA-4 therapy against prostate cancer by the combination with STAT3 inhibition.

Male C57BL6 mice were subcutaneously inoculated with the murine prostate cancer cell line RM-1. Tumor progression was monitored following treatment with vehicle, the small molecule STAT3 inhibitor GPB730, anti-CTLA-4 or GPB730 + anti-CTLA-4. Treatment with anti-CTLA-4 or anti-CTLA-4 + GPB730 significantly inhibited tumor growth and enhanced survival compared to vehicle. Combining anti-CTLA-4 treatment with GPB730 resulted in a significantly prolonged survival compared to anti-CTLA-4 alone. GPB730 significantly increased infiltration of CD45 + cells in tumors of anti-CTLA-4-treated mice compared to anti-CTLA-4 alone. The levels of tumor-infiltrating Tregs were significantly decreased and the CD8:Treg ratio significantly increased by GPB730 treatment in combination with anti-CTLA-4 compared to anti-CTLA-4 alone. Immunohistochemical analysis showed a significant increase in CD45-positive cells in anti-CTLA-4 and anti-CTLA-4 + GPB730-treated tumors compared to vehicle or GPB730 monotherapy. Plasma levels of IL10 were significantly increased by anti-CTLA-4 compared to vehicle but no increase was observed when combining anti-CTLA-4 with GPB730.

In conclusion, STAT3 inhibition by GPB730 enhances the antitumoral activity of anti-CTLA-4 and decreases the intratumoral Treg frequency in a prostate cancer mouse model. These results support the combination of STAT3 inhibition with anti-CTLA-4 therapy to increase clinical responses in patients with prostate cancer.
Clinical Impact of Portal Vein Distance on Computed Tomography for Postoperative Pancreatic Fistula after Pancreatoduodenectomy
Authors: Endo Yutaka , Kitago Minoru , Shinoda Masahiro , Yagi Hiroshi , Abe Yuta , Oshima Go , Hori Shutaro , Yokose Takahiro , Abe Kodai , Takemura Ryo , Ishi Ryota , Kitagawa Yuko
Published: March 2021

Background

Pancreatic fistulas remain a significant concern after pancreatectomy owing to the associated high risk of mortality and high costs. It is not possible to perform preoperative risk stratification for all patients. This study aimed to evaluate the usefulness of the measurement of portal vein (PV) distance as a predictive indicator of pancreatic fistula development after pancreatoduodenectomy and compare it with the usefulness of other indicators such as body mass index (BMI), and abdominal fat area.

Methods

Patient characteristics, preoperative laboratory data, radiographic findings, and their association with pancreatic fistula development after pancreatoduodenectomy were analyzed for 157 patients who underwent resection during 2011–2017. Clinically relevant postoperative pancreatic fistulas (CR‐POPF) were defined as Grade B or C fistulas based on the International Study Group of Pancreatic Surgery (ISGPS) 2016 consensus.

Results

CR‐POPF developed in 38 patients (24.2%). Multivariate logistic regression indicated that PV distance and BMI were potential candidates for predictive models for pancreatic fistula development, and small pancreatic duct diameter, diabetes mellitus development, and pathology of non‐pancreatic cancers were independent factors for CR‐POPF. When comparing the two risk models (PV distance‐ and BMI‐based models), the PV distance‐derived risk model was compatible to the BMI‐based stratification models (area under the curve 0.831 vs. 0.830).

Conclusions

PV distance was confirmed to be a useful risk predictor for CR‐POPF. This research highlighted the efficacy of abdominal thickness measurement, which is simple and easily applicable in the clinical setting.
In vitro models of fetal lung development to enhance research into congenital lung diseases
Authors: Shibuya Soichi , Allen-Hyttinen Jessica , De Coppi Paolo , Michielin Federica
Published: March 2021

Purpose

This paper aims to build upon previous work to definitively establish in vitro models of murine pseudoglandular stage lung development. These can be easily translated to human fetal lung samples to allow the investigation of lung development in physiologic and pathologic conditions.

Methods

Lungs were harvested from mouse embryos at E12.5 and cultured in three different settings, i.e., whole lung culture, mesenchyme-free epithelium culture, and organoid culture. For the whole lung culture, extracted lungs were embedded in Matrigel and incubated on permeable filters. Separately, distal epithelial tips were isolated by firstly removing mesothelial and mesenchymal cells, and then severing the tips from the airway tubes. These were then cultured either in branch-promoting or self-renewing conditions.

Results

Cultured whole lungs underwent branching morphogenesis similarly to native lungs. Real-time qPCR analysis demonstrated expression of key genes essential for lung bud formation. The culture condition for epithelial tips was optimized by testing different concentrations of FGF10 and CHIR99021 and evaluating branching formation. The epithelial rudiments in self-renewing conditions formed spherical 3D structures with homogeneous Sox9 expression.

Conclusion

We report efficient protocols for ex vivo culture systems of pseudoglandular stage mouse embryonic lungs. These models can be applied to human samples and could be useful to paediatric surgeons to investigate normal lung development, understand the pathogenesis of congenital lung diseases, and explore novel therapeutic strategies.
Diet supporting therapy for inflammatory bowel diseases
Authors: Kikut Justyna , Konecka Nina , Ziętek Maciej , Kulpa Danuta , Szczuko Małgorzata
Published: March 2021

Purpose

Non-specific inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. More and more often attention is paid to the possibility of dietary support for inflammatory bowel diseases.

Methods

The following review article considers the role of dietary components in the treatment of IBD as: pteridines, probiotics, bovine immunoglobulin, vitamin D, omega-3, flavonoids, polyphenols, curcumin and phosphatidylcholine. The article also discusses plant raw materials of arjuna, soy protein and nettles, trying to summarize their effect on quenching the inflammatory process within the intestines. This review focuses on the possibilities of dietary components and supplementation use to improve the pharmacotherapy response as well as the general clinical patients’ condition.

Results

The mechanism of action of supportive therapy is based on reduction in oxidative stress, maintaining the adequate balance between Th1 and Th2 lymphocytes by affecting cytokines, increasing riboflavin supply for macrophages, increasing expression of vitamin D receptor, regulation by decreasing the expression of NF-κB in liver cells and ability to inhibit the COX2 entrance and inactivate prostaglandins that are involved in the inflammatory process and 12-lipoxygenase pathway inhibition.

Conclusion

Considering clinical researches, it seems that the use of the above-mentioned ingredients in the diet of patients suffering IBD may positively influence the treatment process and maintenance of remission.
Transferring clinically established immune inflammation markers into exercise physiology: focus on neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index
Authors: Walzik David , Joisten Niklas , Zacher Jonas , Zimmer Philipp
Published: March 2021

Over the last decades the cellular immune inflammation markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII = NLR × platelets) have emerged in clinical context as markers of disease-related inflammation and are now widely appreciated due to their integrative character. Transferring these clinically established inflammation markers into exercise physiology seems highly beneficial, especially due to the low temporal, financial and infrastructural resources needed for assessment and calculation. Therefore, the aim of this review is to summarize evidence on the value of the integrative inflammation markers NLR, PLR and SII for depiction of exercise-induced inflammation and highlight potential applications in exercise settings. Despite sparse evidence, multiple investigations revealed responsiveness of the markers to acute and chronic exercise, thereby opening promising avenues in the field of exercise physiology. In performance settings, they might help to infer information for exercise programming by reflecting exercise strain and recovery status or periods of overtraining and increased infection risk. In health settings, application involves the depiction of anti-inflammatory effects of chronic exercise in patients exhibiting chronic inflammation. Further research should, therefore, focus on establishing reference values for these integrative markers in athletes at rest, assess the kinetics and reliability in response to different exercise modalities and implement the markers into clinical exercise trials to depict anti-inflammatory effects of chronic exercise in different patient collectives.
Transcatheter treatment by valve-in-valve and valve-in-ring implantation for prosthetic tricuspid valve dysfunction
Authors: Dannenberg Varius , Donà Carolina , Koschutnik Matthias , Winter Max-Paul , Nitsche Christian , Kammerlander Andreas A. , Bartko Philipp E. , Hengstenberg Christian , Mascherbauer Julia , Goliasch Georg
Published: March 2021

Valve degeneration after surgical tricuspid valve replacement or repair is frequent and may require repeat replacement/repair. For high-risk patients, transcatheter valve-in-valve and valve-in-ring procedures have emerged as valuable treatment alternatives. Preprocedural transthoracic echocardiography is the method of choice to detect malfunction of the prosthesis including degenerative stenosis and/or regurgitation requiring reintervention. Subsequently, computed tomography is helpful for detailed anatomical analysis and periprocedural planning. Device selection and sizing depend on the size and structural details of the implanted ring or prosthesis. The procedure is mainly guided by fluoroscopy; however, transesophageal echocardiography provides complementary guidance during device implantation. Preferred access route is the right femoral vein but in cases of more horizontal implants a jugular approach might be feasible. Suitable transcatheter valves are the Edwards Sapien 3 and the Medtronic Melody valves. Differences in surgical prostheses or annuloplasty implants are important for device selection, height consideration and additional ballooning prior to or after implantation. Transesophageal echocardiography postimplantation is convenient for the assessment of transvalvular gradients or paravalvular leaks.
Micro-architectural analysis of in-memory OLTP: Revisited
Authors: Sirin Utku , Tözün Pınar , Porobic Danica , Yasin Ahmad , Ailamaki Anastasia
Published: March 2021

Micro-architectural behavior of traditional disk-based online transaction processing (OLTP) systems has been investigated extensively over the past couple of decades. Results show that traditional OLTP systems mostly under-utilize the available micro-architectural resources. In-memory OLTP systems, on the other hand, process all the data in main-memory and, therefore, can omit the buffer pool. Furthermore, they usually adopt more lightweight concurrency control mechanisms, cache-conscious data structures, and cleaner codebases since they are usually designed from scratch. Hence, we expect significant differences in micro-architectural behavior when running OLTP on platforms optimized for in-memory processing as opposed to disk-based database systems. In particular, we expect that in-memory systems exploit micro-architectural features such as instruction and data caches significantly better than disk-based systems. This paper sheds light on the micro-architectural behavior of in-memory database systems by analyzing and contrasting it to the behavior of disk-based systems when running OLTP workloads. The results show that, despite all the design changes, in-memory OLTP exhibits very similar micro-architectural behavior to disk-based OLTP: more than half of the execution time goes to memory stalls where instruction cache misses or the long-latency data misses from the last-level cache (LLC) are the dominant factors in the overall execution time. Even though ground-up designed in-memory systems can eliminate the instruction cache misses, the reduction in instruction stalls amplifies the impact of LLC data misses. As a result, only 30% of the CPU cycles are used to retire instructions, and 70% of the CPU cycles are wasted to stalls for both traditional disk-based and new generation in-memory OLTP.
Fourier extension estimates for symmetric functions and applications to nonlinear Helmholtz equations
Authors: Weth Tobias , Yeşil Tolga
Published: March 2021

We establish weighted$$L^p$$Lp-Fourier extension estimates for$$O(N-k) \times O(k)$$O(N-k)×O(k)-invariant functions defined on the unit sphere$${\mathbb {S}}^{N-1}$$SN-1, allowing for exponentspbelow the Stein–Tomas critical exponent$$\frac{2(N+1)}{N-1}$$2(N+1)N-1. Moreover, in the more general setting of an arbitrary closed subgroup$$G \subset O(N)$$G⊂O(N)andG-invariant functions, we study the implications of weighted Fourier extension estimates with regard to boundedness and nonvanishing properties of the corresponding weighted Helmholtz resolvent operator. Finally, we use these properties to derive new existence results forG-invariant solutions to the nonlinear Helmholtz equation$$\begin{aligned} -\Delta u - u = Q(x)|u|^{p-2}u, \quad u \in W^{2,p}({\mathbb {R}}^{N}), \end{aligned}$$-Δu-u=Q(x)|u|p-2u,u∈W2,p(RN),whereQis a nonnegative bounded andG-invariant weight function.
Overestimation of grey matter atrophy in glioblastoma patients following radio(chemo)therapy
Authors: Gommlich A. , Raschke F. , Petr J. , Seidlitz A. , Jentsch C. , Platzek I. , van den Hoff J. , Kotzerke J. , Beuthien-Baumann B. , Baumann M. , Krause M. , Troost E. G. C.
Published: March 2021

Objective

Brain atrophy has the potential to become a biomarker for severity of radiation-induced side-effects. Particularly brain tumour patients can show great MRI signal changes over time caused by e.g. oedema, tumour progress or necrosis. The goal of this study was to investigate if such changes affect the segmentation accuracy of normal appearing brain and thus influence longitudinal volumetric measurements.

Materials and methods

T1-weighted MR images of 52 glioblastoma patients with unilateral tumours acquired before and three months after the end of radio(chemo)therapy were analysed. GM and WM volumes in the contralateral hemisphere were compared between segmenting the whole brain (full) and the contralateral hemisphere only (cl) with SPM and FSL. Relative GM and WM volumes were compared using paired t tests and correlated with the corresponding mean dose in GM and WM, respectively.

Results

Mean GM atrophy was significantly higher for full segmentation compared to cl segmentation when using SPM (mean ± std: ΔVGM,full = − 3.1% ± 3.7%, ΔVGM,cl = − 1.6% ± 2.7%; p < 0.001, d = 0.62). GM atrophy was significantly correlated with the mean GM dose with the SPM cl segmentation (r = − 0.4, p = 0.004), FSL full segmentation (r = − 0.4, p = 0.004) and FSL cl segmentation (r = -0.35, p = 0.012) but not with the SPM full segmentation (r = − 0.23, p = 0.1).

Conclusions

For accurate normal tissue volume measurements in brain tumour patients using SPM, abnormal tissue needs to be masked prior to segmentation, however, this is not necessary when using FSL.
Accurate discretization of poroelasticity without Darcy stability
Authors: Mardal Kent-Andre , Rognes Marie E. , Thompson Travis B.
Published: March 2021

In this manuscript we focus on the question: what is the correct notion of Stokes–Biot stability? Stokes–Biot stable discretizations have been introduced, independently by several authors, as a means of discretizing Biot’s equations of poroelasticity; such schemes retain their stability and convergence properties, with respect to appropriately defined norms, in the context of a vanishing storage coefficient and a vanishing hydraulic conductivity. The basic premise of a Stokes–Biot stable discretization is: one part Stokes stability and one part mixed Darcy stability. In this manuscript we remark on the observation that the latter condition can be generalized to a wider class of discrete spaces. In particular: a parameter-uniform inf-sup condition for a mixed Darcy sub-problem is not strictly necessary to retain the practical advantages currently enjoyed by the class of Stokes–Biot stable Euler–Galerkin discretization schemes.
Golub–Kahan vs. Monte Carlo: a comparison of bidiagonlization and a randomized SVD method for the solution of linear discrete ill-posed problems
Authors: Bai Xianglan , Buccini Alessandro , Reichel Lothar
Published: March 2021

Randomized methods can be competitive for the solution of problems with a large matrix of low rank. They also have been applied successfully to the solution of large-scale linear discrete ill-posed problems by Tikhonov regularization (Xiang and Zou in Inverse Probl 29:085008, 2013). This entails the computation of an approximation of a partial singular value decomposition of a large matrixAthat is of numerical low rank. The present paper compares a randomized method to a Krylov subspace method based on Golub–Kahan bidiagonalization with respect to accuracy and computing time and discusses characteristics of linear discrete ill-posed problems that make them well suited for solution by a randomized method.
Magnetic nanocarriers as a therapeutic drug delivery strategy for promoting pain-related motor functions in a rat model of cartilage transplantation
Authors: Zhang Xingyu , Yang Jianjun , Cheng Baochang , Zhao Shenli , Li Yao , Kang Hui , Chen Shiyi
Published: March 2021

Cartilage is an avascular tissue with low cellularity and insufficient self-repair response. In clinical practice, a large articular cartilage defect is usually fixed by cartilage transplantation. Importantly, the fast repair process has been demanded postoperatively in the area between the host cartilage and the transplanted cartilage. In the past few years, magnetic nanoparticles have drawn great attention due to their biocompatible, biodegradable, and nontoxic properties. In addition, the nanoparticles can easily pass through the cell plasma membrane and increase the cellular uptake efficiency. Here, a therapeutic drug delivery strategy was proposed for cartilage repair. The prepared kartogenin (KGN)-conjugated magnetic nanocarriers (KGN@NCs) promoted the viability of chondrocytes in vitro. In a rat model of cartilage transplantation, intra-articularly delivered KGN@NCs generated cartilage with a flat surface and a high level of aggrecan in vivo. Notably, KGN@NCs were also capable of improving the pain-related motor functions. They promoted the motor functional parameters including the print area and intensity to restore to a normal level compared with the single KGN. Therefore, these therapeutic drug nanocarriers provided the potential for cartilage repair.
Cultivating quality awareness in corona times
Authors: Timmerman Guus , Baart Andries , den Bakker Jan
Published: March 2021

The Covid-19 pandemic is a tragedy for those who have been hard hit worldwide. At the same time, it is also a test of concepts and practices of what good care is and requires, and how quality of care can be accounted for. In this paper, we present our Care-Ethical Model of Quality Enquiry (CEMQUE) and apply it to the case of residential care for older people in the Netherlands during the Covid-19 pandemic. Instead of thinking about care in healthcare and social welfare as a set of separate care acts, we think about care as a complex practice of relational caring, crossed by other practices. Instead of thinking about professional caregivers as functionaries obeying external rules, we think about them as practically wise professionals. Instead of thinking about developing external quality criteria and systems, we think about cultivating (self-)reflective quality awareness. Instead of abstracting from societal forces that make care possible but also limit it, we acknowledge them and find ways to deal with them. Based on these critical insights, the CEMQUE model can be helpful to describe, interrogate, evaluate, and improve existing care practices. It has four entries: (i) the care receiver considered from their humanness, (ii) the caregiver considered from their solicitude, (iii) the care facility considered from its habitability and (iv) the societal, institutional and scholarly context considered from the perspective of the good life, justice and decency. The crux is enabling all these different entries with all their different aspects to be taken into account. In Corona times this turns out to be more crucial than ever.
Interpretations of Spinoza in early Russian Marxism
Authors: Steila Daniela
Published: March 2021

The roots of the controversial readings of Spinoza during Soviet times date back to the history of Russian Marxism. Spinoza was a most influential figure whom different Marxist currents and thinkers wanted to have on their side. This article examines the most relevant interpretations. First, it sketches some fundamental traits of Plekhanov’s understanding of Spinoza’s ontology and epistemology, from his critique of German revisionism at the end of the 1890s to his polemics against empiriocriticism and its Russian impact. Spinoza was a particularly relevant and authoritative thinker for the so-called “Machists” as well, and some of their different interpretations are analyzed as representing their critical approach to Marxism. Finally, Lunacharskiiʼs discussion is considered as a peculiar alternative to Plekhanov’s orthodox understanding not only of Spinoza but of Marxism itself. While Plekhanov judged Spinoza’s “theological” language a relic of his epoch, Lunacharskii maintained that it was precisely his “religious” feelings that made Spinoza a forerunner of Marxism.
The social myth and human domination of nature in Georg Sorel and Stanisław Brzozowski
Authors: Kasprzak Krystof
Published: March 2021

In this article I aim to bring to the fore a problematic trait of Polish philosopher Stanisław Brzozowski’s (1878–1911) thinking, which is his insistence on the metaphysical importance of human domination of nature through work, technology, and maximization of production. The focal point of the article is Brzozowski’s interpretation of Georg Sorel, with an emphasis on Reflections on Violence and the concept of the social myth. I argue that Brzozowski considers the primary strength of the social myth to lie in its contribution to such domination, because its principal trait is to provide man with a sublime feeling of elevation above nature. Furthermore, this feeling becomes a motive force for struggle against nature. In conclusion, I suggest that the perspective of the sublime is a fruitful path for future critical encounters with Brzozowski’s work. The first part of the article stresses the importance of the sublime in Reflections on Violence. Sorel uses this concept throughout his main work to describe the affective nature of the violence of the social myth, which coordinates the inclinations of the masses towards emancipation. The second part discusses how Brzozowski understands the social myth, law, and nationhood from the perspective of human domination of elemental nature.
Tailings Transport System Design Using Probabilistic Methods
Authors: Stowe Josh , Farrell Ian , Wingeard Eric
Published: March 2021

Tailings transport system design is generally based on identifying the minimum and maximum process boundary conditions for pump selection and pipeline sizing. The approach is robust and well-proven. However, the approach has the potential to skew selections to operating scenarios that have a very low likelihood of occurring, such as the combination of high solids throughput and low tailings solids concentration. The approach can result in a tailings transport system design that is overly conservative. A probabilistic method-based approach captures the independent variability of design inputs and the combined likelihood of outcomes. This approach identifies the process conditions that have the highest likelihood of occurrence and are most applicable to equipment and pipeline selections. An outline of a probabilistic-based approach to tailings transport system design and the resulting selections is provided in this article. The probabilistic-based system design is compared to the outcomes from the traditional approach. The benefits and challenges to this approach are discussed and recommendations for utilizing this approach for tailings transport system design are provided.
50565 CTSA collaboration to support K-12 school re-opening in the COVID-19 pandemic
Authors: Inkelas Moira , Arah Onyebuchi A. , Manuel Vladimir G. , Nianogo Roch , Morrison Douglas E. , Anderson Nathaniel , Yilmaz Defne , Kuo Tony
Published: March 2021

ABSTRACT IMPACT: The mobilization of a CTSA-sponsored team with multi-disciplinary translational science expertise enabled the university to provide a range of T1-T4 expertise to a large, complex school district that resulted in permanent learning and data science infrastructure. OBJECTIVES/GOALS: The Clinical Translational Science Institute (CTSI) formed a multidisciplinary science team to provide expertise in support of the re-opening of in-person learning in the second-largest U.S. school district during the COVID-19 pandemic. METHODS/STUDY POPULATION: The assembled interdisciplinary science team provided expertise in epidemiology, machine learning, causal inference and agent-based modeling, data and improvement science, biostatistics, clinical and laboratory medicine, health education, community engagement, and experience in outbreak investigation and management. The team included TL1 pre and postdoctoral fellows and mobilized scientists from multiple professional schools and T1-T4 stages of translational research. RESULTS/ANTICIPATED RESULTS: Tangible outcomes achieved using this team approach included the development of practical metrics for use in the school community, a learning process, the integration of preventive design elements into a testing and tracing program, and targeted and data-driven health education. The team, for example, generated new data displays for community engagement and collaborated with the school district in their use to visualize, learn from, and act on variation across a 700 square mile region. DISCUSSION/SIGNIFICANCE OF FINDINGS: Novel translational methods can be used to establish a learning environment and data science infrastructure that complements efforts of public health agencies to aid schools in the COVID-19 pandemic. These new capabilities apply to COVID-19 testing and vaccines and can be mobilized for future population health challenges faced by school districts.
41538 Characterizing Opioid Overdose Hotspots for Targeted Overdose Prevention and Treatment
Authors: Samuels Elizabeth A. , Goedel William , Conkey Lauren , Koziol Jennifer , Karim Sarah , Scagos Rachel P. , Keeler Lee Ann Jordison , Yorlets Rachel , Reddy Neha , Becker Sara , Merchant Roland , Marshall Brandon D. L.
Published: March 2021

ABSTRACT IMPACT: Identifying factors associated with opioid overdoses will enable better resource allocation in communities most impacted by the overdose epidemic. OBJECTIVES/GOALS: Opioid overdoses often occur in hotspots identified by geographic and temporal trends. This study uses principles of community engaged research to identify neighborhood and community-level factors associated with opioid overdose within overdose hotspots which can be targets for novel intervention design. METHODS/STUDY POPULATION: We conducted an environmental scan in three overdose hotspots’‘ two in an urban center and one in a small city’‘ identified by the Rhode Island Department of Health as having the highest opioid overdose burden in Rhode Island. We engaged hotspot community stakeholders to identify neighborhood factors to map within each hotspot. Locations of addiction treatment, public transportation, harm reduction programs, public facilities (i.e., libraries, parks), first responders, and social services agencies were converted to latitude and longitude and mapped in ArcGIS. Using Esri Service Areas, we will evaluate the service areas of stationary services. We will overlay overdose events and use logistic regression identify neighborhood factors associated with overdose by comparing hotspot and non-hotspot neighborhoods. RESULTS/ANTICIPATED RESULTS: We anticipate that there will be differing neighborhood characteristics associated with overdose events in the densely populated urban area and those in the smaller city. The urban area hotspots will have overlapping social services, addiction treatment, and transportation service areas, while the small city will have fewer community resources without overlapping service areas and reduced public transportation access. We anticipate that overdoses will occur during times of the day when services are not available. Overall, overdose hotspots will be associated with increased census block level unemployment, homelessness, vacant housing, and low food security. DISCUSSION/SIGNIFICANCE OF FINDINGS: Identifying factors associated with opioid overdoses will enable better resource allocation in communities most impacted by the overdose epidemic. Study results will be used for novel intervention design to prevent opioid overdose deaths in communities with high burden of opioid overdose.
45419 Patient Perceptions of COVID-19 Impact on their Fertility Care
Authors: Dsouza Karen , Orellana Minerva , Ainsowrth Alessandra , Riggan Kirsten A. , Shenoy Chandra , Allyse Megan A.
Published: March 2021

ABSTRACT IMPACT: In alignment with principles of community engaged research, feedback from participants in this research study may influence infertility clinics to offer psychological support for individuals or couples experiencing high levels of psychosocial burden when pursuing fertility procedures, especially during periods of interrupted care or uncertainty. OBJECTIVES/GOALS: 1) To assess the psychosocial impact on patients whose fertility treatments were interrupted during the COVID-19 shutdown. 2) To assess the correlation of patient perceived risk at the time of treatment cessation compared to the resumption of treatment, both during an ongoing pandemic. METHODS/STUDY POPULATION: Female patients with scheduled fertility treatments at Mayo Clinic within 6 months of 3/15/2020, were contacted through the patient portal and invited to participate in this study. Interested patients were contacted by a study staff member to obtain their consent and HIPAA authorization and to schedule a phone or Zoom interview. Semi-structured interviews were conducted individually, or in partner dyads depending upon participant preference, and were recorded with their permission. Audio recordings were professionally transcribed and de-identified. Transcripts were qualitatively analyzed using NVivo 12 based on the principles of grounded theory. RESULTS/ANTICIPATED RESULTS: 26 participants were interviewed; 20 interviews were conducted individually and 3 were conducted in dyads with their partners. Initial themes from the interviews show that COVID-19 compounded existing psychosocial burden on individuals and couples undergoing fertility treatments. Women who were older in age, had prolonged history of infertility, or multiple unsuccessful treatment cycles reported feeling an increased urgency to proceed with fertility treatments due to the time sensitive care, which outweighed the perceived risks of COVID-19 to either themselves or the potential pregnancy. Patients also reported a desire for improved communication regarding their procedures and overall well-being, as well as options for counseling services for individuals or couples undergoing fertility treatments. DISCUSSION/SIGNIFICANCE OF FINDINGS: Participants indicated the need for increased psychological support for patients pursuing fertility treatments, especially during periods of interrupted care or uncertainty, as highlighted during the COVID 19 pandemic. Offering counseling as a routine part of the treatment process may mitigate this burden.
69742 miR-338-5p as a Biomarker of Neuropathic Pain After Spinal Cord Injury
Authors: Kowalski Jesse , Nguyen Nguyen , Battaglino Ricardo , Falci Scott , Charlie Susan , Morse Leslie
Published: March 2021

ABSTRACT IMPACT: Identification of microRNA (miRNA) associated with neuropathic pain after spinal cord injury (SCI) will elucidate underlying epigenetic mechanisms contributing to its development and identify targets for intervention to optimize treatment strategies and outcomes. OBJECTIVES/GOALS: Approximately 70% of individuals with SCI experience neuropathic pain, which is refractory to pharmacologic intervention, and can reduce overall health and wellbeing. This study aims to identify predictive miRNA biomarkers of neuropathic pain after SCI to identify targets for the development of efficacious interventions. METHODS/STUDY POPULATION: Blood samples and clinical outcome measures were collected from adult participants with SCI with neuropathic pain (n = 28) and without neuropathic pain (n = 15). The sample population consisted of a mean age of 39 (SD = 12.12), 8 female (20%), with 13 classified as acute SCI (within 3 months post injury) and 30 as chronic SCI (> 3 years post injury). Pain presence, type, and intensity were assessed with the International Spinal Cord Injury Basic Pain Dataset (ISCIBPDS). Serum miRNA sequencing counts were produced from blood samples. Fold change and independent t-tests assessed differential expression between those with and without neuropathic pain, and those with chronic or acute SCI. Linear regression was performed to explore the relationship between miRNA expression and ISCIBPDS pain intensity ratings. RESULTS/ANTICIPATED RESULTS: In individuals with SCI, significant downregulation of expression of miR-338-5p was present in those with neuropathic pain compared to those without neuropathic pain (fold change = 0.81, p = 0.04). A significant relationship between expression of miR-338-5p and highest reported neuropathic pain intensity on the ISCIBPDS was identified (R2 = 0.15, F = 7.32, p < 0.01). Covariates of sex, age, and years post injury were not found to significantly influence the relationship between miRNA expression and ISCIBPDS intensity ratings. No significant differences in miR-338-5p expression were identified between participants with acute and chronic SCI, or with nociceptive pain ratings, demonstrating specificity of the relationship between miR-338-5p differential expression with pain of a neuropathic nature. DISCUSSION/SIGNIFICANCE OF FINDINGS: These findings, along with validated targets of miR-338-5p in the NF-KB neuroinflammatory signaling pathway, suggest that miR-338-5p may serve a neuroprotective role in modulating neuroinflammation, and that its downregulation may result in maladaptive neuroplastic mechanisms contributing to the development of neuropathic pain after SCI.