Miracle-dz/UniFAR-FTUs huggingface dataset:
The profibrotic effects of MK‐8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway

The discovery of hypoxia‐inducible factor (HIF)‐prolyl hydroxylase inhibitor (PHI) has revolutionized the treatment strategy for renal anemia. However, the presence of multiple transcription targets of HIF raises safety concerns regarding HIF‐PHI. Here, we explored the dose‐dependent effect of MK‐8617 (MK), a kind of HIF‐PHI, on renal fibrosis. MK was administered by oral gavage to mice for 12 wk at doses of 1.5, 5, and 12.5 mg/kg. In vitro, the human proximal tubule epithelial cell line HK‐2 was treated with increasing doses of MK administration. Transcriptome profiling was performed, and fibrogenesis was evaluated. The dose‐dependent biphasic effects of MK on tubulointerstitial fibrosis (TIF) were observed in chronic kidney disease mice. Accordingly, high‐dose MK treatment could significantly enhance TIF. Using RNA‐sequencing, combined with in vivo and in vitro experiments, we found that Krüppel‐like factor 5 (KLF5) expression level was significantly increased in the proximal tubular cells, which could be transcriptionally regulated by HIF‐1α with high‐dose MK treatment but not low‐dose MK. Furthermore, our study clarified that HIF‐1α‐KLF5‐TGF‐β1 signaling activation is the potential mechanism of high‐dose MK‐induced TIF, as knockdown of KLF5 reduced TIF in vivo. Collectively, our study demonstrates that high‐dose MK treatment initiates TIF by activating HIF‐1α‐KLF5‐TGF‐β1 signaling. These findings provide novel insights into TIF induction by high‐dose MK (HIF‐PHI), suggesting that the safety dosage window needs to be emphasized in future clinical applications. —Li, Z. ‐L. , Lv, L. ‐L. , Wang, B. , Tang, T. ‐T. , Feng, Y. , Cao, J.‐Y. , Jiang, L. ‐Q. , Sun, Y. ‐B. , Liu, H. , Zhang, X. ‐L. , Ma, K. ‐L. , Tang, R. ‐N. , Liu, B. ‐C. The profibrotic effects of MK‐8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway. FASEB J. 33, 12630–12643 (2019). www.fasebj. org
The Effects of Transcranial Direct Current Stimulation on Chronic Ankle Instability.

PURPOSE Given maladaptive neuroplasticity following musculoskeletal injury, interventions capable of restoring corticospinal excitability should be considered. We therefore aimed to determine if 4-weeks of anodal transcranial direct current stimulation (aTDCS) with eccentric exercise would improve neural excitability, functional performance, and patient-reported function in individuals with chronic ankle instability (CAI). METHODS Twenty-six individuals with CAI were recruited to undergo 4-weeks of eccentric evertor strengthening. Subjects were randomized into aTDCS (n=13) and sham (n=13) groups, where the aTDCS group received 18-minutes of aTDCS (1.5mA) over the primary motor cortex. Participants were assessed for cortical excitability, dynamic balance & muscle activation, functional performance & strength, and patient-reported function at baseline, week-2, week-4, and week-6. RESULTS Twenty-two subjects completed the training and test sessions. Cortical excitability (resting motor threshold) to peroneus longus in aTDCS increased from baseline (36.92±11.53) to week-6 (32.91±12.33, p=0.024), while sham increased excitability from baseline (36.67±12.74) to week-2 (27.86±14.69, p=0.007), but decreased at week-4 (35.63±13.10, p=0.022) & week-6 (35.99±13.52, p=0.006). Dynamic balance and muscle activation also improved in the aTDCS group from baseline to week-6 (p=0.034). Functional performance on a side-hop test increased in all participants from baseline to week-2 (p=0.003). The aTDCS group had decreased perceived disablement from week-2 (18.09±6.41) to week-4 (15.55±4.82, p=0.046), whereas the sham group reported increased disablement from baseline (17.91±4.59) to week-2 (21.00±8.52, p=0.047). CONCLUSIONS Our results provide preliminary evidence that 4-weeks of eccentric training with aTDCS improves cortical excitability, functional performance, and patient-reported function in individuals with CAI. These data are the first to show the efficacy of non-invasive brain stimulation therapies in patients with musculoskeletal injury, and demonstrates the link between improved neural excitability and functional outcomes.
Resistance of human primary mesenchymal stem cells to cytotoxic effects of nutlin‐3 in vitro

The small‐molecule nutlin‐3 was found to be an effective therapeutic compound and p53 activator, and acts as a murine double minute 2 antagonist, although these findings need to be clinically confirmed. The essential components of the bone marrow include mesenchymal stem cells (MSCs), which play a key role in protecting, regenerating, and proliferating hematopoietic stem cells (HSCs). This feature is vital for HSC after exposure to myelotoxic anticancer agents; nevertheless, the effects of nutlin‐3 on MSCs remain to be disclosed. The present research study was conducted to examine the antiproliferative and proapoptotic effectiveness of nutlin‐3 in bone marrow MSCs (BMSCs).
Anti-inflammatory surface coatings based on polyelectrolyte multilayers of heparin and polycationic nanoparticles of naproxen-bearing polymeric drugs.

Immune response to biomaterials can produce chronic inflammation and fibrosis leading to implant failure, which is related to surface properties of the biomaterials. This work describes the preparation and characterization of polyelectrolyte multilayer (PEM) coatings that combine the anti-inflammatory activity of heparin as polyanion with the potential release of Naproxen a nonsteroidal anti-inflammatory drug from polymeric nanoparticles (NP) with cationic surface charge. The polyelectrolyte multilayers were characterized by physical methods to estimate multilayer growth, thickness, zeta potential and topography. It was found that multilayers with NP had negative zeta potentials and expressed a viscoelastic behavior, while studies of topography showed that nanoparticles formed continuous surface coatings. THP-1-derived macrophages were used to study short-term anti-inflammatory activity (time scale 48 h) showing that PEM that contained heparin reduced cell adhesion and IL1-β secretion, when compared to those with polystyrene sulfonate, used as alternative polyanion in multilayer formation. On the other hand, presence of NP in PEM was related to a reduced foreign body giant cell formation after 15 days, when compared to PEM that contained chitosan as alternative polycation, which suggests a long-term anti-inflammatory effect of Naproxen-containing nanoparticles. It was also shown that macrophages were able to take up NP from multilayers, which indicates a release of Naproxen by digestion of NP in the lysosomal compartment. These findings indicate that surface coatings composed of heparin and Naproxen-based NP on implants like biosensors have the potential to attenuate foreign body reaction after implantation, which may improve the long-term functionality of implants.
Robustness of Clonogenic Assays as a Biomarker for Cancer Cell Radiosensitivity

Photon radiation therapy is a major curative treatment for cancer. However, the lack of robust predictive biomarkers for radiosensitivity precludes personalized radiation therapy. Clonogenic assays are the gold standard method for measuring the radiosensitivity of cancer cells. Although a large number of publications describe the use of clonogenic assays to measure cancer cell radiosensitivity, the robustness of results from different studies is unclear. To address this, we conducted a comprehensive detailed literature search of 256 common cancer cell lines and identified the eight cell lines most-frequently examined for photon sensitivity using clonogenic assays. Survival endpoints and experimental parameters from all 620 relevant experiments were compiled and analyzed. We found that the coefficients of variation for SF2 (surviving fraction after 2 Gy irradiation) and for D10 (dose that yields a surviving fraction of 10%) were below 30% for all cell lines, indicating that SF2 and D10 have acceptable inter-assay precision. These data support further analysis of published data on clonogenic assays using SF2 and D10 as survival endpoints, which facilitates robust identification of biological profiles representative of cancer cell sensitivity to photons.
COMPUTATIONAL MODEL OF A DROPLET GENERATOR USING THE VOF METHOD

Aerogen Vibronic® is a droplet generation technology for pulmonary drug delivery. At the core of the device is a palladium plate, approximately 5 mm in diameter, perforated with approximately 1,000 orifices of ~ 4 μm diameter. The plate vibrates at a frequency of 128 kHz and amplitude of 2.5 μm transverse to the plate. Liquid stored on one side of the plate is pumped through the orifices, producing fine droplets which can reach the deepest areas of the lung [1]. For deep lung penetration, droplet size range of 1-5 μm is required [2]
Near Field Behavior of a Liquid Jet in a Crossflow

The atomization and dispersion of a liquid jet injected into a high speed crossflow is relevant to many engineering applications. Although this problem may appear relatively simple, predicting the liquid jet breakup, dispersion, vaporization, and mixing requires resolving many complex phenomena with high accuracy through either empirical, semi-empirical, or first principles models. In the current work, the nearfield behavior of a liquid jet injected into a high speed crossflow is examined using current state-of-the-art high resolution, high speed shadowgraphy. Results are obtained for three injector diameters for varying Weber number and momentum flux ratios. Issues associated with the calculation of these values are reviewed and the implications relative to discrepancies observed among existing correlations and breakup regime maps are discussed. The results are analyzed to classify the breakup modes of the liquid column and to examine the static and dynamic initial penetration behavior of the liquid jet. The results illustrate the utility of applying advanced visualization diagnostics to reveal rich details associated with the jet breakup processes that cannot be obtained with still images. The results suggest that the mode of breakup of the liquid jet has a weaker dependency upon momentum flux ratio than previously suggested. The results also show that previous correlations developed for average jet penetration describe the penetration in the current study reasonably well. It is reasoned that this good agreement may be due, in part, to the use of geometry similar to those used in these previous studies. In particular, it is reasoned that good agreement can only be expected if the injector discharge coefficients are the same. Finally, analysis associated with the dynamic behavior of the jet as resolved by 1 microsecond exposures and frame rates in excess of 6,500 per second illustrate the ability to detect periodic behavior in the jet breakup process. Corresponding author Background and Objective The injection of liquid into a crossflowing stream has a wide array of applications and has been studied extensively over the past few decades. Despite the extensive work done on this seemingly simple problem, a wide range of interpretation, conclusions and correlations have resulted that often yield significantly differing results regarding breakup regimes, penetration, and effects of fluid properties. By way of example, Figure 1 compares predicted penetration values for a water jet injected into a crossflow at room temperature and atmospheric pressure. The results demonstrate considerable scatter, the reasons for which are not entirely clear.
The role of ICT in tourism and related changes in skills : electronic commerce and revenue management

Traditional tourism value chains evolved into tourism value net. In this new environment tourism professionals need skills to identify opportunities for cross-promotion, skills for finding efficient combination of distribution channels, skills for managing sales across several distribution channels and making profit out of this process. In the tourism value net, revenue management becomes as important and challenging as never before. Effective revenue management requires skills to combine several knowledge areas persistently and creatively.
Optimal design of elastic columns for maximum buckling load

The problem of Lagrange, to nd the curve which by its revolution about an axis in its plane determines the column of greatest e¢ ciency, is examined. A comparison is made between the optimal shapes of the compressed column predicted by several existing formulations for columns of circular cross section hinged at the end points. Then, two di¤erent generalizations of the problem, that follow from a generalized plane elastica and the theory called Kirchho¤s kinetic analogue, are considered. The optimal shape of a compressed column that can su¤er not only exure as in classical elastica theory, but also compression and shear is rst presented. Second, the distribution of material along the length of a compressed and twisted column is optimized so that the column is of minimum volume and will support a given load without spatial buckling. Necessary conditions for both problems are derived using the maximum principle of Pontryagin. The optimal shapes are obtained by numerical integration. The principal novelty of the present results is that both solutions, that follow from two possible generalizations of the classical BernoulliEuler bending theory, lead to the optimum column with non-zero cross sectional area at its ends.
Aristotle's Fish: the case of the kobios and phucis

Aristotle was a remarkable observer of the living world. He made detailed observations on the anatomy and life history characteristics of many organisms as part of a larger study into the differentiae (diaphora) of groups of animals. This reexamination of Aristotle's observations of two small fishes is a study into the work or the way of being of particular organic wholes. As such, it is directed by three main objectives: to evaluate the accuracy of those observations Aristotle makes with regard to the kobios and phucis in the History of Animals, as well as to understand how he might have conducted his research; to determine whether aspects of those observations would ground more philosophical arguments; and to contribute to the understanding of the basic biology of these fishes. In so doing, this article also may introduce a new generation of biologists to the richness of Aristotle's biological observations and the questions that motivated them.
Nutrient Interactions and Toxicity Adult Cockatiels (Nymphicus hollandicus) Metabolically Adapt to High Protein Diets

To determine the ability of cockatiels (Nymphicus hollandicus), a granivorous avian species, to adapt metabolically to high dietary protein levels, adult males (n 5 26) were fed isocaloric diets containing 11, 20, 35 or 70% crude protein (CP) for 11 mo. Throughout the trial, body weight and breast muscle weight were maintained by 11, 20 or 70% CP. The 35% CP diet resulted in significantly greater body weight (P , 0.05) and whole-body lipid content (P , 0.05) compared with the 11% CP diet. The 20% CP diet resulted in greater breast muscle mass compared with 70% CP (P , 0.05). Activity of the amino acid catabolic enzymes alanine aminotransferase, aspartate aminotransferase and arginase as well as the gluconeogenic enzyme phosphoenolpyruvate carboxykinase were significantly increased with 70% CP (P , 0.05). Serum essential amino acids, urea and uric acid were also increased with 70% CP (P , 0.05), but the magnitude of their increase was similar to that found in omnivorous chickens fed a similar diet. There was no evidence of visceral gout, articular gout or renal pathology; however liver lesion severity, and specifically liver lipogranuloma severity, was significantly increased above 11% CP (P , 0.05). We conclude that cockatiels are able to up-regulate enzymes for amino acid catabolism as well as mechanisms for nitrogen excretion in response to high dietary protein levels, and that high dietary protein levels are not associated with kidney dysfunction in this avian species. J. Nutr. 131: 2014–2020, 2001.
Teacher Pay Reform and Productivity: Panel Data Evidence from Adoptions of Q-Comp in Minnesota

This paper studies the impacts of teacher pay-for-performance (P4P) reforms adopted with complementary human resource management (HRM) practices on student achievement and workforce flows. Since 2005, dozens of Minnesota school districts in cooperation with teachers’ unions implemented P4P as part of the state’s Quality Compensation program. Exploiting district variation in participation status and timing, we find evidence that P4P-centered HRM reform raises students’ achievement by 0.03 standard deviations. Falsification tests suggest that gains are causal. They appear to be driven especially by productivity increases among less-experienced teachers.
Income Divergence between Connecticut and Mississippi: Financialization and Uneven Development, 1970–2010

Abstract:In recent decades, income divergence between the richest and poorest states in the United States has occurred, contradicting the prediction of neoclassical theory that income growth rates should converge over time. This article places neoclassical theory in dialogue with alternative bodies of literature: financialization, world cities, and uneven development. Using Mississippi and Connecticut as cases, a decomposition shows income divergence between these two states has been caused by two phenomena related to financialization: a growing geographic concentration of the highest-income households, and an increasing share of income claimed by these households.RESUMEN:En las últimas décadas, se ha producido una divergencia de ingresos entre los estados más ricos y más pobres de los Estados Unidos, lo cual contradice la predicción de la teoría neoclásica de que las tasas de crecimiento de los ingresos deberían converger con el tiempo. Este artículo coloca la teoría neoclásica en diálogo con cuerpos alternativos de literatura: financiarización, ciudades del mundo y desarrollo desigual. Usando Mississippi y Connecticut como casos de estudio, una descomposición muestra que la divergencia de ingresos entre estos dos estados ha sido causada por dos fenómenos relacionados con la financiarización: una creciente concentración geográfica de hogares con mayores ingresos y una proporción cada vez mayor del ingreso reclamado por estos hogares.
Benzonatate Exposure Trends and Adverse Events.

BACKGROUND AND OBJECTIVES Adverse events (AE), including death, occur in children with benzonatate use. This study aims to understand recent trends in benzonatate exposure and clinical consequences in pediatric patients. METHODS This retrospective analysis of data from IQVIA pharmacy drug dispensing, National Poison Data System, National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project, FDA Adverse Event Reporting System, and the medical literature evaluated exposure trends and medication-related AEs with benzonatate. Trends for comparator narcotic and nonnarcotic antitussive medications were analyzed where possible for context. RESULTS During the study period, pediatric benzonatate prescription utilization increased but remained low compared with pediatric utilization of dextromethorphan-containing prescription antitussive medications. Among the 4689 pediatric benzonatate exposure cases reported to US poison control centers from 2010 to 2018, 3727 cases (80%) were for single-substance exposures. Of these, 3590 cases (77%) were unintentional exposures and most involved children 0 to 5 years old (2718 cases, 83%). Cases involving intentional benzonatate exposure increased among children 10 to 16 years old with a more pronounced increase for multiple-substance exposures. Most benzonatate cases involving misuse or abuse were for children 10 to 16 years old (59 cases, 61%). The proportion of cases with serious adverse effects was low. There were few cases annually of serious AEs with benzonatate in children. CONCLUSIONS There were rising patterns of unintentional ingestion of benzonatate in children 0 to 5 years old and intentional benzonatate ingestion in children 10 to 16 years old. Rational prescribing and improved provider and caregiver awareness of benzonatate toxic effects may reduce risks associated with benzonatate exposure.
Student Engagement in Higher Education: Theoretical Perspectives and Practical Approaches for Diverse Populations

Geertz is to get close to reality by anchoring research in the context being studied” (p. 550). What a wonderful lesson for all educational researchers to learn; keep research simple, clear, and straightforward and it will appeal to practitioners and scholars alike. Readers of the Journal of College Student Development can benefit from On Higher Education as it provides a solid foundation in higher education both here in the United States and internationally. The breadth and depth of the essays are highly compelling, and in fact, this book could easily be used in a course on institutional governance, organizational change, or higher education in general. Perhaps one of my favorite aspects of this anthology is that Clark put it together with the help of his wife Adele Clark. The two have been partners for decades. As I too have written with my husband and cherish his feedback and support, it was endearing to see Clark acknowledge the person who has been his muse for so many years. Not only are Clark’s essays, hard work, and intellectual curiosity a lesson for all of us, but his care for his partner in life is something for which we should all strive.
Exponential ergodicity of stochastic heat equations with H\"older coefficients

We investigate the stochastic heat equation driven by space-time white noise defined on an abstract Hilbert space, assuming that the drift and diffusion coefficients are both merely H\"older continuous. Random field SPDEs are covered as special examples. We give the first proof that there exists a unique in law mild solution when the diffusion coefficient is $\beta$ - H\"older continuous for $\beta>\frac{3}{4}$ and uniformly non-degenerate, and that the drift is locally H\"older continuous. Meanwhile, assuming the existence of a suitable Lyapunov function for the SPDE, we prove that the solution converges exponentially fast to the unique invariant measure with respect to a typical Wasserstein distance. Our technique generalizes when the SPDE has a Burgers type non-linearity $(-A)^{1/2}F(X_t)$ or $\partial_x F(X_t)$, where $F$ is continuous and has linear growth. We further consider a stochastic reaction diffusion equation that has polynomially growing, not locally Lipschitz coefficients thus not covered by the abstract Hilbert space setting, and we prove existence of a unique solution for such equation via an adapted technique.
Easy to Decide, Hard to Agree: Reducing Disagreements Between Saliency Methods

A popular approach to unveiling the black box of neural NLP models is to leverage saliency methods, which assign scalar importance scores to each input component. A common practice for evaluating whether an interpretability method is faithful has been to use evaluation-by-agreement -- if multiple methods agree on an explanation, its credibility increases. However, recent work has found that saliency methods exhibit weak rank correlations even when applied to the same model instance and advocated for the use of alternative diagnostic methods. In our work, we demonstrate that rank correlation is not a good fit for evaluating agreement and argue that Pearson-$r$ is a better-suited alternative. We further show that regularization techniques that increase faithfulness of attention explanations also increase agreement between saliency methods. By connecting our findings to instance categories based on training dynamics, we show that the agreement of saliency method explanations is very low for easy-to-learn instances. Finally, we connect the improvement in agreement across instance categories to local representation space statistics of instances, paving the way for work on analyzing which intrinsic model properties improve their predisposition to interpretability methods.