Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Vitamin D on the Cardiovascular System in Advanced Chronic Kidney Disease (CKD) and Dialysis Patients

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.
Carrot-or-Stick: How to Trigger the Digitalization of Local Owner Operated Retail Outlets?

Local Owner Operated Retail Outlets (LOOROs) are threatened in their very existence by the digitalization pressure from online and offline competitors on the one hand and by changing shopping habits of their customers on the other. Despite all digitally-enabled opportunities to regain competitive power, LOOROs still hesitate to adopt digital tools and applications. Politicians, city managers and retail lobbies seek for triggers to support the local structures and to push the digitalization efforts of local retailers. Building on Andreoni ́s “Carrot-and-Stick Approach”, this study examines the impact of the availability of resources (carrot) and the perception of pressure (stick) on the use of digital applications among 223 owners of LOOROs from 26 cities in Germany. Our findings show that LOOROs are receptive for “Carrot-andStick”. LOOROs seek for orientation while suffering under a shortage of time and capacities and seem to be disconnected from the development of their competitors and their customers.
Synthesis and evaluation of ortho-[18F] fluorocelecoxib for COX-2 cholangiocarcinoma imaging

Background An 18F-tagged NSAID analog was prepared for use as a probe for COX-2 expression, which is associated with tumor development. Methods The in vivo uptake of celecoxib was monitored with ortho-[18F]fluorocelecoxib using positron emission tomography (PET). The binding affinity of ortho-[18F]fluorocelecoxib to COX-1 and COX-2 enzymes were assessed using the competitor celecoxib. Results The IC50 values were 0.039 μM and 0.024 μM, respectively. A selectivity index of 1.63 was obtained (COX-2 vs COX-1). COX-2 overexpressed cholangiocarcinoma (CCA) murine cells took up more ortho-[18F]fluorocelecoxib than that by usual CCA cells from 10 to 60 minutes post incubation. Competitive inhibition (blocking) of the tracer uptake of ortho-[18F]fluorocelecoxib in the presence of celecoxib by the COX-2 overexpressed CCA cells and the usual CCA cells gave the IC50 values of 0.5 μM and 46.5 μM, respectively. Based on the in vitro accumulation data and in vivo metabolism half-life (30 min), PET scanning was performed 30–60 min after the administration of ortho-[18F]fluorocelecoxib through the tail vein. Study of ortho-[18F]F-celecoxib in the CCA rats showed a tumor to normal ratio (T/N) of 1.38±0.23 and uptake dose of 1.14±0.25 (%ID/g). Conclusion The inferior in vivo blocking results of 1.48±0.20 (T/N) and 1.18±0.22 (%ID/g) suggests that the nonspecificity is associated with the complex role of peroxidase or the binding to carbonic anhydrase.
Complex Queries Optimization and Evaluation over Relational and NoSQL Data Stores in Cloud Environments

The production of huge amount of data and the emergence of cloud computing have introduced new requirements for data management. Many applications need to interact with several heterogeneous data stores depending on the type of data they have to manage: relational and NoSQL (i.e., document, graph, key-value, and column) data stores. Interacting with heterogeneous data models via different APIs and query languages imposes challenging tasks to the developers of multiple data stores applications. Indeed, the execution of complex queries over heterogeneous data models cannot, currently, be achieved in a declarative way as it is used to be with single data store application, and therefore requires extra implementation efforts. In this paper we propose a mediation based component to optimize and execute complex queries over multiple data stores in Cloud environments. This component is referred to as virtual data store (VDS). The key ingredients of our solution are (1) a simple global schema describing the different data sources and their relationships, (2) a cost model to evaluate the cost of the operations, (3) an inter data stores parallelism execution model, and (4) a dynamic programming based approach to generate optimal execution plan. Quantitative and qualitative experiments are conducted to validate our approach.
CACF

Emerging Resistive Random Access Memory (ReRAM) is a promising candidate as the replacement for DRAM due to its low standby power, high density, high scalability, and nonvolatility. By employing the unique crossbar structure, ReRAM can be constructed with extremely high density. However, the crossbar ReRAM faces some serious challenges in terms of performance, reliability, and energy consumption. First, ReRAM’s crossbar structure causes an IR drop problem due to wire resistance and sneak currents, which results in nonuniform access latency in ReRAM banks and reduces its reliability. Second, without access transistors in the crossbar structure, write disturbance results in serious data reliability problem. Third, the access latency, reliability, and energy use of ReRAM arrays are significantly influenced by the data patterns involved in a write operation. To overcome the challenges of the crossbar ReRAM, we propose a novel circuit architecture co-optimization framework for improving the performance, reliability, and energy use of ReRAM-based main memory system, called CACF. The proposed CACF consists of three levels, including the circuit level, circuit architecture level, and architecture level. At the circuit level, to reduce the IR drops along bitlines, we propose a double-sided write driver design by applying write drivers along both sides of bitlines and selectively activating the write drivers. At the circuit architecture level, to address the write disturbance with low overheads, we propose a RESET disturbance detection scheme by adding disturbance reference cells and conditionally performing refresh operations. At the architecture level, a region partition with address remapping method is proposed to leverage the nonuniform access latency in ReRAM banks, and two flip schemes are proposed in different regions to optimize the data patterns involved in a write operation. The experimental results show that CACF improves system performance by 26.1%, decreases memory access latency by 22.4%, shortens running time by 20.1%, and reduces energy consumption by 21.6% on average over an aggressive baseline. Meanwhile, CACF significantly improves the reliability of ReRAM-based memory systems.
On Minrank and Forbidden Subgraphs

The minrank over a field F of a graph G on the vertex set { 1,2,… ,n} is the minimum possible rank of a matrix M ∈ Fn × n such that Mi, i ≠ 0 for every i, and Mi, j =0 for every distinct non-adjacent vertices i and j in G. For an integer n, a graph H, and a field F, let g(n,H, F) denote the maximum possible minrank over F of an n-vertex graph whose complement contains no copy of H. In this article, we study this quantity for various graphs H and fields F. For finite fields, we prove by a probabilistic argument a general lower bound on g(n,H,F), which yields a nearly tight bound of Ω (√ n/ log n) for the triangle H=K3. For the real field, we prove by an explicit construction that for every non-bipartite graph H, g(n,H, R) ≥ nδ for some δ = δ (H)> 0. As a by-product of this construction, we disprove a conjecture of Codenotti et al. [11]. The results are motivated by questions in information theory, circuit complexity, and geometry.
Screening of acetylcholinesterase inhibitors in marine organisms from the Caribbean Sea

Abstract The acetylcholinesterase inhibitory activity of 89 organic extracts from marine organisms was evaluated through a TLC bioautography methodology. Extracts from soft corals (Eunicea and Plexaura) were the most active compared with extracts from sponges. The bioguided chemical study of the most active extract, obtained from Pseudoplexaura porosa, led to the isolation of a diterpene with spectroscopic properties consistent to those published to the cembrane Steylolide. However, further analysis by X-ray diffraction indicated that the compound was the 14-acetoxycrassine (1), correcting the structure reported to the Styelolide. Additionally, the acetylcholinesterase inhibitory activity of fourteen cembranoids (2–15) isolated from soft corals Eunicea knighti and Pseudoplexaura flagellosa was evaluated. Cembranoids 2, 3 and 4 were the most active compounds in the TLC bioassay. Then, the most promising cembranoids, 14-acetoxycrassine (1) and asperdiol (2), were tested quantitatively and they exhibited IC50 values of 1.40 ± 0.113 and 0.358 ± 0.130 μM, respectively.
Kane's method-based dynamic modeling and triple-trajectory tracking of a hyper redundant non-holonomic MDAMS

Kinematic and dynamic modelings of a hyperredundant non-holonomic mobile dual-arm manipulator system (MDAMS) are computation consuming and complex. Firstly, in this paper, the forward kinematics are formulated using the modified Denavit Hartenberg (MDH) method. Besides, a task priority-based redundancy solving method with joint limit avoidance is introduced. In total, four ordered variables are defined to deal with the motion coordination among the mobile base (MB) and the end-effectors (EE), and two compact relative Jacobian matrices are formulated to characterize the relative motions for the proposed MDAMS. Secondly, Kane's method is employed to dynamically model the MDAMS with more than 20 components because of its advantages over Euler-Lagrange (E-L) formulations. Then, a triple-trajectory-based semi-decentralized control strategy is proposed with a kinematic control law for the MB. Moreover, the physical tip-over avoidance is analyzed and the tracking stability is proven using the back-stepping technique. Finally, a mathematical model is built and trajectory tracking tasks are numerically simulated to validate the model.
Preventive Effect of Antioxidative Nutrient-Rich Enteral Diet Against Liver Ischemia and Reperfusion Injury.

BACKGROUND Liver ischemia and reperfusion injury (IRI) is a major problem associated with liver surgery. This study is aimed to compare the preventive effect of an antioxidative nutrient-rich enteral diet (Ao diet) with an ordinal enteral diet (control diet) against liver IRI. METHODS The Ao diet was an ordinary diet comprising polyphenols (catechin and proanthocyanidin) and enhanced levels of vitamins C and E. Male C57BL/6 mice were fed the Ao or control diet for 7 days before ischemic insult for 60 minutes, followed by reperfusion for 6 hours. The levels of inflammatory cytokines, chemokines, and antioxidant enzymes and oxidative stress were evaluated. RESULTS After 7 days of pretreatment with the Ao diet, the serum levels of vitamins C and E in mice were markedly elevated. The levels of serum aspartate aminotransferase and alanine aminotransferase, as well as the scores of liver necrosis caused by ischemia and reperfusion, were significantly lower in the Ao diet group than in the control diet group. The gene expression levels of inflammatory cytokines and chemokines, such as interleukin-6 and CXCL1, were significantly lower in the Ao diet group. In the liver, the levels of antioxidant enzymes superoxide dismutase 1 (SOD1) and SOD2 were significantly higher and the malondialdehyde levels were significantly lower in the Ao diet group. Cell adhesion molecule expression was significantly lower, and neutrophil and macrophage infiltration was less in the Ao diet group. CONCLUSIONS Antioxidative nutrient supplementation to an ordinary enteral diet may mitigate liver IRI by causing an antioxidant effect and suppressing inflammation.
Insight into the substrate specificity change caused by the Y227H mutation of α-glucosidase III from the European honeybee (Apis mellifera) through molecular dynamics simulations

Honey from the European honeybee, Apis mellifera, is produced by α-glucosidases (HBGases) and is widely used in food, pharmaceutical, and cosmetic industries. Categorized by their substrate specificities, HBGases have three isoforms: HBGase I, II and III. Previous experimental investigations showed that wild-type HBGase III from Apis mellifera (WT) preferred sucrose to maltose as a substrate, while the Y227H mutant (MT) preferred maltose to sucrose. This mutant can potentially be used for malt hydrolysis because it can efficiently hydrolyze maltose. In this work, to elucidate important factors contributing to substrate specificity of this enzyme and gain insight into how the Y227H mutation causes substrate specificity change, WT and MT homology models were constructed, and sucrose/maltose was docked into active sites of the WT and MT. AMBER14 was employed to perform three independent molecular dynamics runs for these four complexes. Based on the relative binding free energies calculated by the MM-GBSA method, sucrose is better than maltose for WT binding, while maltose is better than sucrose for MT binding. These rankings support the experimentally observed substrate specificity that WT preferred sucrose to maltose as a substrate, while MT preferred maltose to sucrose, suggesting the importance of binding affinity for substrate specificity. We also found that the Y227H mutation caused changes in the proximities between the atoms necessary for sucrose/maltose hydrolysis that may affect enzyme efficiency in the hydrolysis of sucrose/maltose. Moreover, the per-residue binding free energy decomposition results show that Y227/H227 may be a key residue for preference binding of sucrose/maltose in the WT/MT active site. Our study provides important and novel insight into the binding of sucrose/maltose in the active site of Apis mellifera HBGase III and into how the Y227H mutation leads to the substrate specificity change at the molecular level. This knowledge could be beneficial in the design of this enzyme for increased production of desired products.
Adversarial confidence and smoothness regularizations for scalable unsupervised discriminative learning

In this paper, we consider a generic probabilistic discriminative learner from the functional viewpoint and argue that, to make it learn well, it is necessary to constrain its hypothesis space to a set of non-trivial piecewise constant functions. To achieve this goal, we present a scalable unsupervised regularization framework. On the theoretical front, we prove that this framework is conducive to a factually confident and smooth discriminative model and connect it to an adversarial Taboo game, spectral clustering and virtual adversarial training. Experimentally, we take deep neural networks as our learners and demonstrate that, when trained under our framework in the unsupervised setting, they not only achieve state-of-the-art clustering results but also generalize well on both synthetic and real data.
Measuring Influence on Instagram: A Network-Oblivious Approach

This paper focuses on the problem of scoring and ranking influential users of Instagram, a visual content sharing online social network (OSN). Instagram is the second largest OSN in the world with 700 million active Instagram accounts, 32% of all worldwide Internet users. Among the millions of users, photos shared by more influential users are viewed by more users than posts shared by less influential counterparts. This raises the question of how to identify those influential Instagram users. In our work, we present and discuss the lack of relevant tools and insufficient metrics for influence measurement, focusing on a network oblivious approach and show that the graph-based approach used in other OSNs is a poor fit for Instagram. In our study, we consider user statistics, some of which are more intuitive than others, and several regression models to measure users' influence.
Aspergillus fumigatus Inhibits Pseudomonas aeruginosa in Co-culture: Implications of a Mutually Antagonistic Relationship on Virulence and Inflammation in the CF Airway

Many cystic fibrosis (CF) airway infections are considered to be polymicrobial and microbe–microbe interactions may play an important role in disease pathology. Pseudomonas aeruginosa and Aspergillus fumigatus are the most prevalent bacterial and fungal pathogens isolated from the CF airway, respectively. We have previously shown that patients co-colonized with these pathogens had comparable outcomes to those chronically colonized with P. aeruginosa. Our objective was to examine the interactions between A. fumigatus and P. aeruginosa, specifically the effects of co-colonization on biofilm formation, virulence and host pro-inflammatory responses. Our findings suggest that co-infections of A. fumigatus and P. aeruginosa in the Galleria mellonella acute infection model showed that pre-exposure of larvae to sub-lethal inocula of A. fumigatus increased the mortality caused by subsequent P. aeruginosa infection. Co-infection of human bronchial epithelial cells (CFBE41o-) with both pathogens did not enhance IL-6 and IL-8 production beyond the levels observed following single infections. In addition, both pathogens stimulated cytokine secretion via the same two mitogen-activated protein kinases (MAPKs) signaling pathways, ERK and p38. Mixed species biofilms showed overall reduced biofilm development with crystal violet staining. Quantification by species-specific qPCR revealed that both pathogens had mutually antagonistic effects on each other. A. fumigatus supernatants showed strong anti-Pseudomonal activity and gliotoxin was the main active agent. Gliotoxin resulted in varying levels of anti-biofilm activity toward other bacteria commonly found in the CF airways. Gliotoxin produced by A. fumigatus colonizing the CF airways may have a significant impact on the CF airway microbiome composition with potential clinical implications.
Workload Management in Database Management Systems: A Taxonomy

Workload management is the discipline of effectively monitoring, managing and controlling work flow across computing systems. In particular, workload management in database management systems (DBMSs) is the process or act of monitoring and controlling work (i.e., requests) executing on a database system in order to make efficient use of system resources in addition to achieving any performance objectives assigned to that work. In the past decade, workload management studies and practice have made considerable progress in both academia and industry. New techniques have been proposed by researchers, and new features of workload management facilities have been implemented in most commercial database products. In this paper, we provide a systematic study of workload management in today's DBMSs by developing a taxonomy of workload management techniques. We apply the taxonomy to evaluate and classify existing workload management techniques implemented in the commercial databases and available in the recent research literature. We also introduce the underlying principles of today's workload management technology for DBMSs, discuss open problems, and outline some research opportunities in this research area.
Neural Correlates for Intrinsic Motivational Deficits of Schizophrenia; Implications for Therapeutics of Cognitive Impairment

The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT), one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT), not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia.
Community Pharmacy Use by Children across Europe: A Narrative Literature Review

The use of community pharmacies across Europe has potential to alleviate the burden on overstretched healthcare providers. Children and young people (0–18 years) account for a large number of primary care attendances. This narrative literature review between January 2000 and December 2017 examines the use of community pharmacy by paediatric patients in Europe. The results report both positive and negative perceptions of community pharmacy by parents and children, opportunities for an extended role in Europe, as well as the need for further training. The main limitations were the inclusion of English language papers only and an initial review of the literature carried out by a single researcher. It remains to be seen whether a ‘new-look’ role of the community pharmacist is practical and in alignment with specific European Commission and national policies.
FIMCE

Virtualization-based memory isolation has been widely used as a security primitive in various security systems to counter kernel-level attacks. In this article, our in-depth analysis on this primitive shows that its security is significantly undermined in the multicore setting when other hardware resources for computing are not enclosed within the isolation boundary. We thus propose to construct a fully isolated micro-computing environment (FIMCE) as a new primitive. By virtue of its architectural niche, FIMCE not only offers stronger security assurance than its predecessor, but also features a flexible and composable environment with support for peripheral device isolation, thus greatly expanding the scope of applications. In addition, FIMCE can be integrated with recent technologies such as Intel Software Guard Extensions (SGX) to attain even stronger security guarantees. We have built a prototype of FIMCE with a bare-metal hypervisor. To show the benefits of using FIMCE as a building block, we have also implemented four applications which are difficult to construct using the existing memory isolation method. Experiments with these applications demonstrate that FIMCE imposes less than 1% overhead on single-threaded applications, while the maximum performance loss on multithreaded applications is bounded by the degree of parallelism at the processor level.