Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical and genetic dissection of the RNA-binding surface of the FinO domain of Escherichia coli ProQ

RNA-binding proteins play important roles in bacterial gene regulation through interactions with both coding and non-coding RNAs. ProQ is a FinO-domain protein that binds a large set of RNAs in Escherichia coli, though the details of how ProQ binds these RNAs remain unclear. In this study, we used a combination of in vivo and in vitro binding assays to confirm key structural features of E. coli ProQ’s FinO domain and explore its mechanism of RNA interactions. Using a bacterial three-hybrid assay, we performed forward genetic screens to confirm the importance of the concave face of ProQ in RNA binding. Using gel shift assays, we directly probed the contributions of ten amino acids on ProQ binding to seven RNA targets. Certain residues (R58, Y70, and R80) were found to be essential for binding of all seven RNAs, while substitutions of other residues (K54 and R62) caused more moderate binding defects. Interestingly, substitutions of two amino acids (K35, R69), which are evolutionarily variable but adjacent to conserved residues, showed varied effects on the binding of different RNAs; these may arise from the differing sequence context around each RNA’s terminator hairpin. Together, this work confirms many of the essential RNA-binding residues in ProQ initially identified in vivo and supports a model in which residues on the conserved concave face of the FinO domain such as R58, Y70 and R80 form the main RNA-binding site of E. coli ProQ, while additional contacts contribute to the binding of certain RNAs.
Hybrid vacuum-atmosphere compressors for ultrafast, high-peak power chirped-pulse amplification

Theoretical and experimental results are presented for ultrafast, chirped-pulse amplifier compressors that contain only the final, high-peak power grating in vacuum. The designs are compact and the adjustments of the compressor gratings are at atmosphere. The optical aberrations and dispersion of the system are found to be negligible for the compression of 25-fs pulses. The application of the hybrid vacuum-atmosphere compressor is robust with respect to a broad range of wavelengths and optical configurations.
Immune Profile of Exosomes in African American Breast Cancer Patients Is Mediated by Kaiso/THBS1/CD47 Signaling

Simple Summary African American (AA) women with breast cancer are more likely to have higher inflammation and a stronger overall immune response than European American (EA) women. In this report, we demonstrate the biological role of Kaiso in the immune signaling of breast cancer exosomes. Our findings indicate that Kaiso directly represses tumor suppressor THBS1, and this is associated with increased expression of CD47 and signal regulatory protein (SIRPA). Kaiso depletion attenuated tumor formation in athymic nude mice, and this is associated with increased infiltration of M1 macrophages. In vitro studies using THP1 cells that were treated with exosomes from Kaiso-depleted cells polarize towards the M1 phenotype with increased phagocytosis of cancer cells compared to high Kaiso control exosome, which polarizes towards an M2 phenotype. In summary, these findings reveal that Kaiso modulates the macrophage-mediated immune escape of cancer cells through exosome signaling, which may be related to poorer outcomes, especially for AA women. Abstract African American (AA) women with breast cancer are more likely to have higher inflammation and a stronger overall immune response, which correlate with poorer outcomes. In this report, we applied the nanostring immune panel to identify differences in inflammatory and immune gene expression by race. We observed a higher expression of multiple cytokines in AA patients compared to EA patients, with high expression of CD47, TGFB1, and NFKB1 associated with the transcriptional repressor Kaiso. To investigate the mechanism associated with this expression pattern, we observed that Kaiso depletion results in decreased expression of CD47, and its ligand SIRPA. Furthermore, Kaiso appears to directly bind to the methylated sequences of the THBS1 promotor and repress gene expression. Similarly, Kaiso depletion attenuated tumor formation in athymic nude mice, and these Kaiso-depleted xenograft tissues showed significantly higher phagocytosis and increased infiltration of M1 macrophages. In vitro validation using MCF7 and THP1 macrophages treated with Kaiso-depleted exosomes showed a reduced expression of immune-related markers (CD47 and SIRPA) and macrophage polarization towards the M1 phenotype compared to MCF7 cells treated with exosomes isolated from high-Kaiso cells. Lastly, analysis of TCGA breast cancer patient data demonstrates that this gene signature is most prominent in the basal-like subtype, which is more frequently observed in AA breast cancer patients.
Incidence and Risk Factors for Development of Cardiac Toxicity in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia

Simple Summary The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. We observed a high incidence of cardiac events (58.5%) among 525 treated patients, coupled with significant mortality due to cardiotoxicity (3.6%). The presence of relevant cardiac antecedents was the main risk factor for developing fatal cardiac events (hazard ratio (HR) = 1.9). Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. We observed that, among 285 intensive therapy patients, median overall survival was decreased in those experiencing grade 3–4 cardiac events (p < 0.001). We identified prognostic factors that increase the risk of cardiac events, which may be useful in selecting high-risk patients for stringent cardiac monitoring and management. Abstract The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. Among 571 newly diagnosed AML patients, 26 (4.6%) developed fatal cardiac events, and among 525 treated patients, 19 (3.6%) experienced fatal cardiac events (CI: 2% at 6 months; 6.7% at 9 years). Prior heart disease was associated with the development of fatal cardiac events (hazard ratio (HR) = 6.9). The CI of non-fatal cardiac events was 43.7% at 6 months and 56.9% at 9 years. Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. The 9-year CI of grade 1–2 QTcF prolongation was 11.2%, grade 3 was 2.7%, and no patient had grade 4–5 events. The 9-year CI of grade 1–2 cardiac failure was 1.3%, grade 3–4 was 15%, and grade 5 was 2.1%; of grade 1–2, arrhythmia was 1.9%, grade 3–4 was 9.1%, and grade 5 was 1%. Among 285 intensive therapy patients, median overall survival decreased in those experiencing grade 3–4 cardiac events (p < 0.001). We observed a high incidence of cardiac toxicity associated with significant mortality in AML.
Current Antibiotic Use Among Hospitals in the sub-Saharan Africa Region; Findings and Implications

Background The rapid rise in antimicrobial resistance (AMR) globally, impacting on morbidity, mortality and costs with sub-Saharan African countries reporting the greatest burden is a concern. Instigation of antimicrobial stewardship programs (ASPs) can improve antibiotic use in hospitals and reduce AMR. Implementing ASPs requires knowledge of antibiotic utilization against agreed quality indicators with the data obtained from point prevalence surveys (PPS), hence the need to document antibiotic utilization patterns in sub-Saharan Africa. Methods A narrative review to document current utilization patterns, challenges, indicators and ASPs across sub-Saharan Africa based on previous reviews by the authors, supplemented by the considerable knowledge and experience of the co-authors. Results Results from multiple PPS studies showed a high prevalence of antibiotic use among hospitals, mostly over 50%. Prevalence rates ranged from as low as 37.7% in South Africa to as high as 80.1% in Nigeria. There was also considerable prescribing of broad-spectrum antibiotics which could be due to lack of facilities within hospitals, alongside concerns with co-payments to perform microbiological tests, resulting in empiric prescribing. This is a concern alongside lack of guidelines or adherence to guidelines, which was as low as 4% in one study. Another concern was the high rates of extended prophylaxis to prevent surgical site infections (SSIs), with antibiotics often prescribed for longer than 24 hours, usually multiple doses. Several quality indicators have been used to evaluate antibiotic utilization providing exemplars for the future. Among the initiatives being instigated to improve antibiotic use, ASPs have proved effective. For ASPs to be successful objectives and indicators must be agreed, and regular audits undertaken. Conclusion Antibiotic prescribing across Africa is characterised by high prevalence, usually empirical. Various prescribing and quality indicators are being employed to assess antibiotic use, and ASPs have shown to improve antibiotic prescribing providing direction to reduce AMR.
Small-scale dynamo in cool main-sequence stars

Context: Some of the small-scale solar magnetic flux can be attributed to a small-scale dynamo (SSD) operating in the near-surface convection. The SSD fields have consequences for solar granular convection, basal flux, and chromospheric heating. A similar SSD mechanism is expected to be active in the near-surface convection of other cool main-sequence stars, but this has not been investigated thus far. Aim: We aim to investigate changes in stratification and convection due to inclusion of SSD fields for F3V, G2V, K0V, and M0V spectral types in the near-surface convection. Methods: We studied 3D magnetohydrodynamic (MHD) models of the four stellar boxes, covering the subsurface convection zone up to the lower photosphere in a small Cartesian box, based on the MURaM radiative-MHD simulation code. We compared the SSD runs against reference hydrodynamic runs. Results: The SSD is found to efficiently produce magnetic field with energies ranging between 5% to 80% of the plasma kinetic energy at different depths. This ratio tends to be larger for larger Teff . The relative change in density and gas pressure stratification for the deeper convective layers due to SSD magnetic fields is negligible, except for the Fstar. For the F-star, there is a substantial reduction in convective velocities due to Lorentz force feedback from magnetic fields, which, in turn, reduces the turbulent pressure. Conclusion: The SSD in near-surface convection for cool main-sequence stars introduces small but significant changes in thermodynamic stratification (especially for the F-star) due to a reduction in the convective velocities.
Connection between the three-block generalized Riccati equation and the standard Riccati equation

Nikoukhah et al. (1992) developed a maximum likelihood descriptor Kalman filter the properties of which are governed by a three-block generalized Riccati difference equation (GRDE). The convergence of this GRDE has been studied and the generalization of the eigenvector approach to solving the associated generalized algebraic Riccati equation has been carried out. In this paper, the authors connect the GRDE to the standard Riccati equation to point out Nikoukhah's results from well-known results obtained in standard Kalman filtering. Moreover, while the previous study provides only sufficient conditions on the convergence and stability of the three-block descriptor Kalman filter, the relationship established herein allows the authors to derive necessary and sufficient conditions. In addition, several descriptor Kalman filtering problems can be treated as in the standard case. >
Study on nonlinear dynamics model method for landslide forecasting in Xintan

Based on the dynamic characteristics of nonlinear modeling method, combined with the observed data and numerical calculation, the model of nonlinear gray forecasting and the model of nonlinear chaotic forecasting are established. Through inversion and optimization, an inverse calculation result can be found. It is verified from an illustration that the computed results are in good agreement with the observed data.
The common welfare human resource management system and innovativeness: the mediating role of altruism

PurposeThe paper analyzes and develops Chiva's (2014) proposal on the common welfare HRM system and uncovers its relationship with innovativeness, using altruism as a mediator.Design/methodology/approachThe common welfare HRM system implies a certain human and organizational development of the classic control and commitment HRM systems, and its main goal is to promote innovation through a prosocial approach. To this end, the authors investigated its HRM practices, developed a measurement instrument and provided initial illustrative evidence of some of its main implications for innovativeness and altruism. They tested these relationships on a sample of 269 Spanish firms using structural equations and bootstrapping to confirm the significance of the mediated effect.FindingsResults confirm the study’s hypotheses, thus supporting the common welfare HRM system as a relevant tool for developing innovativeness through the power of altruism. This paper therefore provides empirical evidence of these relationships.Practical implicationsThis study has implications that can help managers to increase innovativeness through a specific HRM system. The findings reveal that a coherent set of HRM practices based on common welfare principles and a high level of consciousness creates a climate of altruism that results in innovativeness.Originality/valueThis research shows that humanistic HRM practices also have an impact on performance variables such as innovativeness, through altruistic employees' behaviors. It also develops a measurement instrument for the common welfare HRM system and provides some initial illustrative evidence of some of its main implications.
Application of Metacognitive Planning Scaffolding for the Cultivation of Computational Thinking

Computational thinking is a way of thinking that helps people “think like a computer scientist” to solve practical problems. However, practicing computational thinking through programming is dependent on the problem solvers’ metacognition. This study investigated students’ metacognitive planning and problem-solving performance in programming through two quantitative studies. First, we analyzed the performance of metacognitive planning and of problem solving through the programming of 21 freshmen, and found that the metacognitive planning performance related to “problem description” and “program comprehension” was significantly correlated with problem-solving performance. Second, semi-scaffolding and full-scaffolding were designed based on the first study. Another 89 freshmen were randomly divided into three groups and were asked to write their programming plan with no-scaffolding, semi-scaffolding, or with full-scaffolding. ANCOVA revealed that the problem-solving performance of the no-scaffolding group was significantly weaker than that of the other two groups, but there was no significant difference between the semi-scaffolding and the full-scaffolding groups. The study indicated that semi-scaffolding had a similar effect to full-scaffolding on problem-solving performance. The study suggests that teachers should emphasize supporting students’ “problem description” and “program comprehension” using semi-scaffolding. This scaffolding technique is sufficient and efficient for training students’ computational thinking through problem solving in programming.
Quantifying Non-Gaussian Water Diffusion by Means of Pulsed-Field-Gradient MRI

J. H. Jensen, J. A. Helpern New York University School of Medicine, New York, New York, United States SYNOPSIS The extent to which water transport in a tissue deviates from homogeneous, Gaussian diffusion can be quantified by a dimensionless statistical measure referred to as the excess kurtosis. By using pulsed-field-gradient spin echo MRI data acquired with large diffusion sensitizing gradients, we show how to estimate the excess kurtosis. In particular, the excess kurtosis can be approximately determined from the lower order terms of an expansion in the gradient strength of the logarithm of the signal intensity. This result is applied to estimate the excess kurtosis in healthy adult and newborn human brain and ischemic rat brain tissue.
Study of parametric effect on laser directed energy deposited Austenitic steel and Inconel functionally graded material

In this paper, the effect of process parameter on functionally graded materials (FGMs) of Inconel 625 (IN625) and Austenitic steel (SS304L) deposited by laser directed energy deposition (LDED) are investigated. For this purpose, FGM walls of different gradient of mix of IN625 and SS304L at different layers are deposited on Austenitic steel (SS316L) substrate at different sets of process parameters. For this study, the process parameters considered are laser power (PL): 1000, 1300 and 1600 W, and scanning speed (v): 0.3, 0.5 and 0.7 m/min. Deposited samples are then subjected to different tests such as energy dispersive spectroscopy (EDS), microhardness, scanning electron microscopy (SEM), X-ray diffraction (XRD), optical microscopy (OM), and nanoindentation. Tests performed on the samples revealed different effects of parameters on the deposition of the FGM wall. Based on the comparison of results of mechanical and metallurgical tests, it is observed that either at PL = 1300 W and/or v = 0.5 m/min, among the considered process parameters, show comparatively better results than the others.
Matching and morphing of isometric models

We present an approach to find dense point-to-point correspondences between two deformed surfaces corresponding to different postures of the same non-rigid object in a fully automatic way. The approach requires no prior knowledge about the shapes being registered or the initial alignment of the shapes. We consider surfaces that are represented by possibly incomplete triangular meshes. We model the deformations of an object as isometrics. To solve the correspondence problem, our approach maps the intrinsic geometries of the surfaces into a low-dimensional Euclidean space via multi-dimensional scaling. This allows us to compute a number of candidate correspondences. The best candidate correspondence is found based on a deformation cost.
An empirical interpolation approach to reduced basis approximations for variational inequalities

ABSTRACT Variational inequalities (VIs) are pervasive in mathematical modelling of equilibrium and optimization problems in engineering and science. Examples of applications include traffic network equilibrium problems, financial equilibrium, obstacle problems, lubrication phenomena and many others. Since these problems are computationally expensive to solve, we focus here on the development of model order reduction techniques, in particular the reduced basis technique. Reduced basis techniques for the approximation of solutions to elliptic VIs have been developed in the last few years. These methods apply to VIs of the so-called first kind, i.e. problems that can be equivalently described by a minimization of a functional over a convex set. However, these recent approaches are inapplicable to VIs of the so-called second kind, i.e. problems that involve minimization of a functional containing non-differentiable terms. In this article, we evaluate the feasibility of using the reduced basis method (RBM) combined with the empirical interpolation method (EIM) to treat VIs. In the proposed approach, the problem is approximated using a penalty or barrier method, and EIM is then applied to the penalty or barrier term. Numerical examples are presented to assess the performance of the proposed method, in particular the accuracy and computational efficiency of the approximation. Although the numerical examples involve only VIs of the first kind, we also evaluate the feasibility of using the RBM combined with the EIM to treat VIs of the second kind.
Inhibition of GSK-3β Enhances Osteoblast Differentiation of Human Mesenchymal Stem Cells through Wnt Signalling Overexpressing Runx2

Small-molecule-inhibitor-based bone differentiation has been recently exploited as a novel approach to regulating osteogenesis-related signaling pathways. In this study, we identified 1-Azakenpaullone, a highly selective inhibitor of glycogen synthase kinase-3β (GSK-3β), as a powerful inducer of osteoblastic differentiation and mineralization of human mesenchymal stem cells (MSCs). GSK-3β is a serine-threonine protein kinase that plays a major role in different disease development. GSK-3β is a key regulator of Runx2 activity in osteoblastic formation. We evaluated alkaline phosphatase activity and staining assays to assess osteoblast differentiation and Alizarin Red staining to assess the mineralization of cultured human MSCs. Gene expression profiling was assessed using an Agilent microarray platform, and bioinformatics were performed using Ingenuity Pathway Analysis software. Human MSCs treated with 1-Azakenpaullone showed higher ALP activity, increased in vitro mineralized matrix formation, and the upregulation of osteoblast-specific marker gene expression. Global gene expression profiling of 1-Azakenpaullone-treated human MSCs identified 1750 upregulated and 2171 downregulated mRNA transcripts compared to control cells. It also suggested possible changes in various signaling pathways, including Wnt, TGFβ, and Hedgehog. Further bioinformatics analysis employing Ingenuity Pathway Analysis recognized significant enrichment in the 1-Azakenpaullone-treated cells of genetic networks involved in CAMP, PI3K (Complex), P38 MAPK, and HIF1A signaling and functional categories associated with connective tissue development. Our results suggest that 1-Azakenpaullone significantly induced the osteoblastic differentiation and mineralization of human MSCs mediated by the activation of Wnt signaling and the nuclear accumulation of β-catenin, leading to the upregulation of Runx2, a key transcription factor that ultimately promotes the expression of osteoblast-specific genes. Thus, 1-Azakenpaullone could be used as an osteo-promotor factor in bone tissue engineering.
Categorical Foundations for Extended Compositional Distributional Models of Meaning

Compositional distributional models of meaning were introduced by Coecke et al. (2010, 2013) with the aim of reconciling the theory of distributional meaning in terms of vector space semantics with the theory of compositional interpretation as one finds it in typelogical grammars. The particular typelogical formalisms employed by Coecke et al. (pregroup grammars, Lambek calculus) have a recognizing capacity equivalent to context-free grammars. It is well known, however, that natural languages exhibit patterns that require expressivity beyond context-free (Huybregts, 1984; Shieber, 1987). The aim of this thesis, then, is to investigate extensions of compositional distributional models of meaning that result from using typelogical grammars with enhanced expressivity. To this end, we give a categorical characterization of the Lambek-Grishin Calculus (see Moortgat (2007, 2009) and references there) and its constituting subsystems in terms of linear distributive categories borrowing a categorification technique from Lambek (1968). We develop a language to reason graphically about morphism structure and equality in terms of string diagrams. Finally, we show that finite-dimensional vector spaces are also an instance of linear distributive categories, which creates the possibility of extended compositional distributional models of meaning.