Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of BMP2 and EZH2 inhibition to stimulate osteogenesis in a 3D bone reconstruction model.

Introduction High concentrations of bone morphogenetic protein 2 (BMP2) in bone regeneration cause adverse events (e.g, heterotopic bone formation and acute inflammation). This study examines novel epigenetic strategies (i.e., EZH2 inhibition) for augmenting osteogenesis thereby aiming to reduce the required BMP2 dose in vivo for bone regeneration and minimize these adverse effects. Methods Human bone marrow-derived mesenchymal stem cells (BMSCs) were grown on 3D-printed medical-grade PCL scaffolds and incubated in osteogenic media containing 50ng/mL BMP2 and/or 5μM GSK126 (EZH2 inhibitor) for 6 days (n=3 per group and time point). Constructs were harvested for RTqPCR analysis at Day 10 and immunofluorescence (IF) microscopy at Day 28. After pre-treating for 6 days and maintaining in osteogenic media for 4 days, BMSC-seeded scaffolds were also implanted in an immunocompromised subcutaneous murine model (n=39; 3/group/donor and 3 control scaffolds) for histological analysis at 8 weeks. Results Pre-treatment of BMSCs with BMP2 and BMP2/GSK126 co-stimulated expression of osteoblast-related genes (e.g., IBSP, SP7, RUNX2 and DLX5), as well as protein accumulation (e.g., collagen Type 1/COL1A1 and osteocalcin/BGLAP) based on immunofluorescence staining. While in vivo implantation for 8 weeks did not result in bone formation, increased angiogenesis was observed in BMP2 and BMP2/GSK126 groups. Conclusions This study finds that BMP2 and GSK126 co-stimulate osteogenic differentiation of MSCs on 3D scaffolds in vitro and may contribute to enhanced vascularization when implanted in vivo to support bone formation. Thus, epigenetic priming with EZH2 inhibitors may have translational potential in bone healing by permitting a reduction of BMP2 dosing in vivo to mitigate its side effects.
Acrolein: A Potential Mediator of Oxidative Damage in Diabetic Retinopathy

Diabetic retinopathy (DR) is the leading cause of vision loss among working-age adults. Extensive evidences have documented that oxidative stress mediates a critical role in the pathogenesis of DR. Acrolein, a product of polyamines oxidation and lipid peroxidation, has been demonstrated to be involved in the pathogenesis of various human diseases. Acrolein’s harmful effects are mediated through multiple mechanisms, including DNA damage, inflammation, ROS formation, protein adduction, membrane disruption, endoplasmic reticulum stress, and mitochondrial dysfunction. Recent investigations have reported the involvement of acrolein in the pathogenesis of DR. These studies have shown a detrimental effect of acrolein on the retinal neurovascular unit under diabetic conditions. The current review summarizes the existing literature on the sources of acrolein, the impact of acrolein in the generation of oxidative damage in the diabetic retina, and the mechanisms of acrolein action in the pathogenesis of DR. The possible therapeutic interventions such as the use of polyamine oxidase inhibitors, agents with antioxidant properties, and acrolein scavengers to reduce acrolein toxicity are also discussed.
Integration of the Drug–Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts

The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from various sources including publications, databases, and other web-based sources in one resource. These drug, gene, and interaction claims are normalized and grouped to identify aliases, merge concepts, and reduce redundancy. The information contained in this resource is available to users through a straightforward search interface, an application programming interface (API), and TSV data downloads. DGIdb 4.0 is the latest major update of this database. Seven new sources have been added, bringing the total number of sources included to 41. Of the previously aggregated sources, 15 have been updated. DGIdb 4.0 also includes improvements to the process of drug normalization and grouping of imported sources. Other notable updates include further development of automatic jobs for routine data updates, more sophisticated query scores for interaction search results, extensive manual curation of interaction source link outs, and the inclusion of interaction directionality. A major focus of this update was integration with crowd-sourced efforts, including leveraging the curation activities of Drug Target Commons, using Wikidata to facilitate term normalization, and integrating into NDEx for producing network representations.
A Rice Immunophilin Homolog, OsFKBP12, Is a Negative Regulator of Both Biotic and Abiotic Stress Responses

A class of proteins that were discovered to bind the immunosuppressant drug FK506, called FK506-binding proteins (FKBPs), are members of a sub-family of immunophilins. Although they were first identified in human, FKBPs exist in all three domains of life. In this report, a rice FKBP12 homolog was first identified as a biotic stress-related gene through suppression subtractive hybridization screening. By ectopically expressing OsFKBP12 in the heterologous model plant system, Arabidopsis thaliana, for functional characterization, OsFKBP12 was found to increase susceptibility of the plant to the pathogen, Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). This negative regulatory role of FKBP12 in biotic stress responses was also demonstrated in the AtFKBP12-knockout mutant, which exhibited higher resistance towards Pst DC3000. Furthermore, this higher-plant FKBP12 homolog was also shown to be a negative regulator of salt tolerance. Using yeast two-hybrid tests, an ancient unconventional G-protein, OsYchF1, was identified as an interacting partner of OsFKBP12. OsYchF1 was previously reported as a negative regulator of both biotic and abiotic stresses. Therefore, OsFKBP12 probably also plays negative regulatory roles at the convergence of biotic and abiotic stress response pathways in higher plants.
The Anticoagulant Therapy for Otogenic Sigmoid Sinus Thrombophlebitis: A Case Report and Literature Review

Sigmoid sinus thrombophlebitis is a severe and potentially fatal intracranial complication of acute otitis media and middle ear cholesteatoma. Early administration of broad-spectrum antibiotics and immediate radical mastoidectomy are the recommended standard treatments; however anticoagulant therapy is always an option worthy of clinical consideration. Here, we report a case of middle ear cholesteatoma complicated with sigmoid sinus thrombophlebitis in a patient who received anticoagulant therapy for 1 year before the operation because of the coronavirus disease 2019 pandemic.
Rheology of Malaysian Tualang honey

KEYWORDS: INTRODUCTION: Malaysian Tualang Honey is a pure honey from combs of Asian honey bees (Apis dorsata) which build their hives high up in the Tualang tree (Koompassia excelsa). The objective of this work was to study the rheological properties of the T ualang honey and the data obtained will be optimized in the development of pharmaceutical products. MATERIALS AND METHOD: There were two types of Tualang honey tested. Pure Tualang honey and oven dried Tualang honey. The oven dried honey was filtered, dehumidified and oven dried at 40oC by FAMA to reduce the water content less than 20%. Tualang honey was investigated for its rheological properties and evaluated at different temperatures (25°C, 37°C and 40°C). The effect of temperatures on rheological properties needs to be documented because of a wide range of temperatures encountered during processing and storage of pharmaceutical products. RESULTS AND DISCUSSION: The curves constructed showed the shear stress was directly proportionate to the shear rate. In a plot of shear rate against shear stress, both types of Tualang honey produced linearity with straight line passed through origin in all temperatures. The viscosity remains constant throughout the range of shear rate in the rheogram of viscosity against shear rate. These profiles were coherent with behaviour of a simple fluid which is Newtonian fluid. The lowest temperature of Tualang honey had the highest shear stress and viscosity. CONCLUSION: These results suggested that Malaysian Tualang honey is a Newtonian fluid. Eventhough the viscosity decreases with increased temperature but the fluid behaviour was not impaired by reduction in water content. The Newtonian behavior of Tualang honey and its effect on the temperatures are expected to facilitate the process of Tualang honey into pharmaceutical products.
14.7 NUMERICAL SIMULATION OF CONVECTIVE EVOLUTION ACROSS LAKE MICHIGAN DURING A WIDESPREAD LAKE-EFFECT SNOW EVENT by

Lake-effect snowstorms generally form in convective boundary layers as cold air flows over relatively warm lakes in fall and winter. This study presents simulations of the evolution of the thermodynamic and microphysical boundary layer structure and mesoscale convective patterns across Lake Michigan for an intense lake-effect event observed during the Lake-Induced Convection Experiment (Lake-ICE, Kristovich et al., 2000) on 13 January 1998. Kristovich et al. (2003) recently published an observational study of this case.
Modeling Turning Points In Global Equity Market

Turning points in financial markets are often characterized by changes in the direction and/or magnitude of market movements with short-to-long term impacts on investors' decisions. This paper develops a Bayesian technique to turning point detection in financial equity markets. We derive the interconnectedness among stock market returns from a piece-wise network vector autoregressive model. The empirical application examines turning points in global equity market over the past two decades. We also compare the COVID-19 induced interconnectedness with that of the global financial crisis in 2008 to identify similarities and the most central market for spillover propagation.
Analysis of the effect of multi-level urban form on bikeshare demand: Evidence from seven large metropolitan areas in the United States

Bikeshare programs in their current form have been in place for several years in many cities across the United States. Encouraging people to use bikeshare for their daily routine travel has numerous social, economic, environmental, and health benefits. Therefore, it is important to understand factors influencing bikeshare use in different urban areas to improve the system and encourage more use. This paper investigates how the built environment at both local and regional scales influences bikeshare use in seven large metropolitan areas in the U.S. The study areas include Boston, Chicago, Philadelphia, Minneapolis, San Francisco, San Jose, and Washington, D.C., and the data consists of about 12 million bike trips from approximately 2,000 stations over a one-year period. In addition to linear regression models built for each individual city for comparison purposes, a multi-level mixed effect regression model is built to predict the number of trips originated from each station with respect to the local and regional built environment pattern. The results are consistent with previous research on the effect of land use at the local level on bikeshare demand and show that residential density, regional diversity, pedestrian-oriented road network density, and job accessibility via transit all have a significant positive effect on bikeshare demand. At the regional level, results suggest that the overall level of mixed-use development and overall bike-friendliness in the region (i.e., exclusive bike routes, right-of-way, and bike facilities) and higher congestion level in the region are significant factors influencing bikeshare activities and demand. Models developed in this study could be applied to other communities that are seeking to improve and/or expand their bikeshare systems, as well as cities planning to launch new bikeshare programs.
Complexity and the Reform Process∗

Decision makers called to evaluate and approve a reform, proposed by an interest group, a politician, or a bureaucracy, suffer from a double asymmetric information problem: about the competence of the proposer and the consequences of the proposal. Moreover, the ability of decision makers to evaluate proposals depends on the complexity of the legislative environment, itself a product of past reforms. We model the strategic interaction between reformers and decision makers as a function of legislative complexity, and study the dynamics of endogenous complexity and stability of reforms. Complexification-simplification cycles can occur on the equilibrium path, and expected long-run complexity may be higher when competence of reform proposers is lower. The results apply to regulatory reforms, legislative politics, and institutional design.
Learning Dynamics and Support for Economic Reforms: Why Good News Can Be Bad

Support for economic reforms has often shown puzzling dynamics: many reforms that began successfully lost public support. This paper shows that learning dynamics can rationalize this paradox because the process of revealing reform outcomes is an example of sampling without replacement. This concept challenges the conventional wisdom that one should begin by revealing reform winners. It may also lead to situations in which reforms that enjoy both ex ante and ex post majority support will still not come to completion. The framework can be used to explain why gradual reforms worked well in China (where successes in Special Economic Zones facilitated further reform), whereas this was much less the case for Latin American and Central and Eastern European countries.
Organizing recurrent network dynamics by task-computation to enable continual learning

Biological systems face dynamic environments that require continual learning. It is not well understood how these systems balance the tension between ﬂexibility for learning and robustness for memory of previous behaviors. Continual learning without catastrophic interference also remains a challenging problem in machine learning. Here, we develop a novel learning rule designed to minimize interference between sequentially learned tasks in recurrent networks. Our learning rule preserves network dynamics within activity-deﬁned subspaces used for previously learned tasks. It encourages dynamics associated with new tasks that might otherwise interfere to instead explore orthogonal subspaces, and it allows for reuse of previously established dynamical motifs where possible. Employing a set of tasks used in neuroscience, we demonstrate that our approach successfully eliminates catastrophic interference and offers a substantial improvement over previous continual learning algorithms. Using dynamical systems analysis, we show that networks trained using our approach can reuse similar dynamical structures across similar tasks. This possibility for shared computation allows for faster learning during sequential training. Finally, we identify organizational differences that emerge when training tasks sequentially versus simultaneously.
Answer to reviewers for manuscript esurf-2017-18 : 10 Be systematics in the Tsangpo-Brahmaputra catchment : the cosmogenic nuclide legacy of the eastern Himalayan syntaxis Reviewer ’ s comment Answer to comment Modification in the manuscript Anonymous Referee # 1

The Tsangpo-Brahmaputra River drains the eastern part of the Himalayan range, and flows from the Tibetan 15 Plateau through the eastern Himalayan syntaxis downstream to the Indo-Gangetic floodplain and the Bay of Bengal. As such, it is a unique natural laboratory to study how denudation and sediment production processes are transferred to river detrital signals. In this study, we present a new Be data set to constrain denudation rates across the catchment and to quantify the impact of rapid erosion within the syntaxis region on cosmogenic nuclide budgets and signals. Be denudation rates span around two orders of magnitude across the catchments (ranging from 0.03 mm/yr to > 4 mm/yr) and sharply 20 increase as the Tsangpo-Brahmaputra flows across the eastern Himalaya. The increase in denudation rates, however, occurs ~150 km downstream of the Namche Barwa-Gyala Peri massif (NBGPm), an area which has been previously characterized by extremely high erosion and exhumation rates. We suggest that this downstream lag is mainly due to the physical abrasion of coarse grained, low Be concentration, landslide material produced within the syntaxis that dilutes the upstream high concentration Be flux from the Tibetan Plateau only after abrasion has transferred sediment to the studied sand fraction. A 25 simple abrasion model produces typical lag distances of 50 to 150 km compatible with our observations. Abrasion effects reduce the spatial resolution over which denudation can be constrained in the eastern Himalayan syntaxis. In addition, we also highlight that denudation rate estimates are dependent on the sediment connectivity, storage, and quartz content of the upstream Tibetan Plateau part of the catchment, which tends to lead to an overestimation of downstream denudations rates. Taking these effects into account we estimate a denudation rates of ca. 2 to 5 mm/yr for the entire syntaxis and ca. 4 to 28 30 mm/yr for the NBGPm, which is significantly higher than other large catchments. Overall, Be concentrations measured at the outlet of the Tsangpo-Brahmaputra in Bangladesh suggest a sediment flux between 780 and 1430 Mt/yr equivalent to a denudation rate between 0.7 and 1.2 mm/yr for the entire catchment.
IP Management in the triple helix context: Evidence from a German research project

Andrea Hanebuth is a researcher with the German Centre for Energy Resources (DER) at the Technische Universtität Bergakademie Freiberg (TU Freiberg). She studied Business Administration and Mechanical Engineering (TUM-BWL) at the Technische Universität München (TUM) and completed her degree as DiplomKauffrau. A doctoral candidate at the Chair of Leadership, Management and Human Resources at TU Freiberg, her research interests include research and innovation management, especially the management of intellectual property, research cooperation models as well as collaborative research management in the context of virtual organization, teams and networks. Current research areas include investigation of alternative models for sustainable research cooperation involving government, industry and science partners, as well as research into management of research groups and organizations characterized by decentralization and under the influence of virtualization.
GEFREASE GErman FRench Equipment for Analysis and Surveillance of biothreats in the Environment (2012-2015)

GEFREASE proposes to answer main issues associated with the detection of potential biological warfare agents. On the basis of previous experience gained by the four project partners, we will develop an integrated diagnostic approach combining on-site detection systems (provisional detection) based on immunoassays and confirmed and precise identification methods based on state-ofthe-art mass spectrometry. We will target both toxins and microorganisms which all belong to the most powerful agents of biological threats.
Partial Replication of Conﬂict-Free Replicated Data Types

Conﬂict-free replicated data types (CRDT) are a class of data structures designed to simplify the operation of distributed systems that require data to be replicated in di ↵ erent nodes. CRDTs are designed in such a way that di ↵ erent replicas can execute concurrent operations in di ↵ erent orders and still converge to the same consistent state when the system becomes quiescent. In this way, CRDTs avoid the coordination costs required for preventing conﬂicts from occurring (such as executing operations in total order) or complex conﬂict resolution procedures. CRDTs are now well understood in the case of full replication, i.e., when all replicas maintain the entire state of the CRDT. However, with CRDTs that store large quantities of data, full replication may be infeasible; one may be forced to shard the CRDT state and let di ↵ erent replicas replicate di ↵ erent shards, i.e., to support partially replicated CRDTs. While classical CRDT algorithms will ensure the consistency of each shard, it may be di � cult to ensure that clients observe a consistent state of the CRDT when they access multiple shards. Also, the data access patterns may require the system to change which nodes replica each shard dynamically. Additionally, in some cases, static partitioning of the CRDT may not be feasible, and it may be useful to dynamically re-allocate objects to shards. In this work, we study ways to express di ↵ erent types of partially-replicated CRDTs, including CRDTS where the number of shards, the assignment of objects to shards, or the number of replicas of each shard may change in runtime. We also propose algorithms to ensure that the use of partial-replication does not a ↵ ect the consistency of the CRDT.
Too-big-to-fail and funding costs: A repository of research studies

Systematic reviews of evaluation studies benefit policy discussions and academic research and are used in many disciplines. In March 2019, the Bank for International Settlements (BIS) thus launched FRAME, a public, online and interactive repository of studies on the effects of financial regulations with an initial focus on the Basel III reforms. This paper describes an extension to this repository with research on the impact of too-big-to-fail (TBTF) reforms on banks’ funding costs. One objective of post-crisis financial sector reforms has been to internalize systemic risk externalities through changes in the funding costs of banks that are classified as being systemically important. The FRAME repository now contains studies on the funding costs of systemically important banks (SIBs), and it currently comprises over 280 quantitative impact estimates from 25 studies.
Statistical Robustness of MCMC Accelerators

—Statistical machine learning often uses probabilistic algorithms, such as Markov Chain Monte Carlo (MCMC), to solve a wide range of problems. Probabilistic computations, often considered too slow on conventional processors, can be accelerated with specialized hardware by exploiting parallelism and optimizing the design using various approximation techniques. Current methodologies for evaluating correctness of probabilistic accelerators are often incomplete, mostly focusing only on end-point result quality (“accuracy”). It is important for hardware designers and domain experts to look beyond end-point “accuracy” and be aware of how hardware optimizations impact statistical properties. This work takes a ﬁrst step toward deﬁning metrics and a methodology for quantitatively evaluating correctness of probabilistic accelerators. We propose three pillars of statistical robustness: 1) sampling quality, 2) convergence diagnostic, and 3) goodness of ﬁt. We apply our framework to a representative MCMC accelerator and surface design issues that cannot be exposed using only application end-point result quality. We demonstrate the beneﬁts of this framework to guide design space exploration in a case study showing that statistical robustness comparable to ﬂoating-point software can be achieved with limited precision, avoiding ﬂoating-point hardware overheads.