Miracle-dz/UniFAR-FTUs huggingface dataset:
Virtual Screening as a Technique for PPAR Modulator Discovery

Virtual screening (VS) is a discovery technique to identify novel compounds with therapeutic and preventive efficacy against disease. Our current focus is on the in silico screening and discovery of novel peroxisome proliferator-activated receptor-gamma (PPARγ) agonists. It is well recognized that PPARγ agonists have therapeutic applications as insulin sensitizers in type 2 diabetes or as anti-inflammatories. VS is a cost- and time-effective means for identifying small molecules that have therapeutic potential. Our long-term goal is to devise computational approaches for testing the PPARγ-binding activity of extensive naturally occurring compound libraries prior to testing agonist activity using ligand-binding and reporter assays. This review summarizes the high potential for obtaining further fundamental understanding of PPARγ biology and development of novel therapies for treating chronic inflammatory diseases through evolution and implementation of computational screening processes for immunotherapeutics in conjunction with experimental methods for calibration and validation of results.
Parallel out-of-core divide-and-conquer techniques with application to classification trees

Classification is an important problem in the field of data mining. Construction of good classifiers is computationally intensive and offers plenty of scope for parallelization. Divide-and-conquer paradigm can be used to efficiently construct decision tree classifiers. We discuss in detail various techniques for parallel divide-and-conquer and extend these techniques to handle efficiently disk-resident data. Furthermore, a generic technique for parallel out-of-core divide-and-conquer problems is suggested. We present pCLOUDS, the parallel version of the decision tree classifier algorithm CLOUDS, capable of handling large out-of-core data sets. pCLOUDS exhibits excellent speedup, sizeup and scaleup properties which make it a competitive tool for data mining applications. We evaluate the performance of pCLOUDS for a range of synthetic data sets on the IBM-SP2.
Meeting inelastic demand in systems with storage and renewable sources

We consider a system where inelastic demand for electric power is met from three sources: the grid, in-house renewables such as wind turbines or solar panels, and an in-house energy storage device. In our setting, power demand, renewable power supply, and cost for grid power are all time-varying and stochastic. Further, there are limits and efficiency issues for charging and discharging the energy storage device. Under such a scenario, at all times across an infinite horizon, we need to determine how to split power demand among the various sources. For that, we formulate an optimization framework that minimizes the long-run average operational cost subject to satisfying demand and meeting capacity constraints. To determine the optimal actions, we construct a dynamic program with parameters estimated from a training data set (that uses real demand, supply and cost data). As the dynamic program is computationally intensive for large-scale problems, we explore an algorithm based on approximate dynamic programming, and apply it to a test data set. We compare its performance against other heuristics that may or may not use the training data. In addition, we ascertain the value of storage as well as the value of installing a renewable source.
Myocardin Is a Key Regulator of CArG-Dependent Transcription of Multiple Smooth Muscle Marker Genes

Abstract— The interactions between serum response factor (SRF) and CArG elements are critical for smooth muscle cell (SMC) marker gene transcription. However, the mechanisms whereby SRF, which is expressed ubiquitously, contributes to SMC-specific transcription are unknown. Myocardin was recently cloned as a coactivator of SRF in the heart, but its role in regulating CArG-dependent expression of SMC differentiation marker genes has not been clearly elucidated. In this study, we examined the expression and the function of myocardin in SMCs. In adult mice, myocardin mRNA was expressed in multiple smooth muscle (SM) tissues including the aorta, bladder, stomach, intestine, and colon, as well as the heart. Myocardin was also expressed in cultured rat aortic SMCs and A404 SMC precursor cells. Of particular interest, expression of myocardin was induced during differentiation of A404 cells, although it was not expressed in parental P19 cells from which A404 cells were derived. Cotransfection studies in SMCs revealed that myocardin induced the activity of multiple SMC marker gene promoters including SM &agr;-actin, SM-myosin heavy chain, and SM22&agr; by 9- to 60-fold in a CArG-dependent manner, whereas myocardin short interfering RNA markedly decreased activity of these promoters. Moreover, adenovirus-mediated overexpression of a dominant-negative form of myocardin significantly suppressed expression of endogenous SMC marker genes, whereas adenovirus-mediated overexpression of wild-type myocardin increased expression. Taken together, results provide compelling evidence that myocardin plays a key role as a transcriptional coactivator of SMC marker genes through CArG-dependent mechanisms.
Nitric oxide mediates lipopolysaccharide‐induced alteration of mitochondrial function in cultured hepatocytes and isolated perfused liver

The influence of endogenous nitric oxide, which is generated by stimulation with lipopolysaccharide, on the mitochondrial energization of rat hepatocytes was investigated in vitro and ex vivo. Using a fluorescence microscope equipped with a silicon intensifier target camera, we visualized fluorescence of rhodamine‐123, a mitochondrial energization–sensitive fluorescence probe, in individual hepatocytes and measured the fluorescence intensity with a digital imaging processor. Although addition of Kupffer cells or lipopolysaccharide in a range of 0.1 to 1.0 νg/ml caused no significant alteration in the fluorescence in hepatocytes, Kupffer cells plus 1.0 μg/ml lipopolysaccharide reduced fluorescence intensity in the cocultured hepatocytes. The alteration of rhodamine‐123 fluorescence in the hepatocytes induced by lipopolysaccharide‐activated Kupffer cells was significantly inhibited by the addition of NG‐monomethyl‐L‐arginine, a selective inhibitor of nitric oxide synthesis. The transportal infusion of lipopolysaccharide also decreased rhodamine‐123 fluorescence in perfused rat liver. The decrease was significantly enhanced in the pericentral regions. Autofluorescence of NADH was elicited by continuous infusion of lipopolysaccharide; this reaction was also enhanced in the pericentral regions. We showed the main site of uptake of infused lipopolysaccharide in the hepatic lobule to be in the periportal regions with fluorescein isothiocyanate–labeled lipopolysaccharide. Our results indicate that the inhibition of mitochondrial energization occurs mainly in pericentral regions, which are distant from the lipopolysaccharide uptake site. The continuous administration of NG‐monomethyl‐L‐arginine significantly attenuated the lipopolysaccharide‐induced decrease in rhodamine‐123 fluorescence and increase of the NADH contents of the hepatic lobule. These results suggest that nitric oxide mediates the lipopolysaccharide‐activated, Kupffer cell–induced inhibition of mitochondrial electron transport in hepatocytes. (HEPATOLOGY 1993;18:380–388).
Bone age: assessment methods and clinical applications

Abstract. The main bone age assessment methods are the Greulich-Pyle and Tanner-Whitehouse 2 methods, both of which involve left hand and wrist radiographs. Several other bone age assessment methods have been developed, including ultrasonographic, computerized, and magnetic resonance (MR) imaging methods. The ultrasonographic method appears unreliable in children with delayed and advanced bone age. MR imaging is noninvasive; however, bone age assessment using MR imaging is relatively new, and further examinations are needed. An automated method for determining bone age, named BoneXpert, has been validated for Caucasian children with growth disorders and children of various ethnic groups. Sex hormones are necessary for bone growth and maturation in children with a bone age corresponding to normal pubertal age, and estrogen is essential for growth plate closure. Bone age is an effective indicator for diagnosing and treating various diseases. A new method for adult height prediction based on bone age has been developed using BoneXpert, in addition to the commonly used Bayley-Pinneau and Tanner-Whitehouse mark II methods. Furthermore, bone age may become a predictor for the timing of peak height velocity and menarche.
UAVs: regulations and law enforcement

ABSTRACT Recent developments in the technology of unmanned aerial vehicles (UAVs) (drones) have opened up important new possibilities in the field of remote sensing. The development of appropriate national legislation has struggled to keep up with these developments. The state of development of this legislation in a number of countries is considered. An important distinction has to be made between the flying of UAVs as a hobby and flying them for commercial work (for present purposes commercial work is defined as commercial/industrial work, scientific research, environmental monitoring, crime detection, etc., in fact any purpose other than just for fun). Rules apply to the flying of a UAV for any purpose whatsoever, even as a hobby. It is becoming increasingly recognized that the pilot of any UAV is responsible for any accident, damage or injury caused by that UAV. More and more countries are requiring that anyone flying a UAV for commercial purposes must have satisfactorily completed a training programme before flying their UAV, and must comply with the relevant rules and keep a log of all flights. There is a problem that there have recently been a sharp increase in airprox incidents (that is near misses between drones (UAVs) and civil aircraft) and a worrying aspect of the situation is that the operator of the drone often cannot be identified. This is leading countries into requiring that all operators of drones should be registered and that their drones should carry a visible identification number that enables the owner/operator to be traced.
UvA-DARE ( Digital Academic Repository ) Strategic innovation in service industries : Managing shifting boundaries

Much of the strategic innovation in service industries can be understood in the context of the shifting boundaries between companies and between firms and their customers. We identify three phases of innovation in modern service industries. All three enabled and triggered by advancements in information technology. The current phase of Service Innovation 3.0 is characterized by open networks between firms and between firms and customers. The paper ends by highlighting a number of dilemmas linked to the challenges of managing service innovation successfully in a world of shifting boundaries and exploding service systems.
Farming data: Testing climatic and palaeoenvironmental effect on Neolithic Adriatic stockbreeding and hunting through zooarchaeological meta-analysis

The possible role of climatic and environmental factors upon the spread and subsequent development of early farming techniques across Europe has long been discussed. We explore the spatial and temporal changes in both animal domestic management techniques and hunting strategies using a meta-analysis of zooarchaeological data from the Neolithic period of the Adriatic Sea (8000–6000 cal. BP). Through a comparison of these patterns with available palaeoenvironmental archives, we conclude that both climatic and environmental factors explain little of the encountered variation and seek for alternative interpretations.
On exact counting and quasi-quantum complexity

We present characterisations of "exact" gap-definable classes, in terms of indeterministic models of computation which slightly modify the standard model of quantum computation. This follows on work of Aaronson [arXiv:quant-ph/0412187], who shows that the counting class PP can be characterised in terms of bounded-error "quantum" algorithms which use invertible (and possibly non-unitary) transformations, or postselections on events of non-zero probability. Our work considers similar modifications of the quantum computational model, but in the setting of exact algorithms, and algorithms with zero error and constant success probability. We show that the gap-definable counting classes [J. Comput. Syst. Sci. 48 (1994), p.116] which bound exact and zero-error quantum algorithms can be characterised in terms of "quantum-like" algorithms involving nonunitary gates, and that postselection and nonunitarity have equivalent power for exact quantum computation only if these classes collapse.
Protection of CpG islands from DNA methylation is DNA-encoded and evolutionarily conserved

DNA methylation is a repressive epigenetic modification that covers vertebrate genomes. Regions known as CpG islands (CGIs), which are refractory to DNA methylation, are often associated with gene promoters and play central roles in gene regulation. Yet how CGIs in their normal genomic context evade the DNA methylation machinery and whether these mechanisms are evolutionarily conserved remains enigmatic. To address these fundamental questions we exploited a transchromosomic animal model and genomic approaches to understand how the hypomethylated state is formed in vivo and to discover whether mechanisms governing CGI formation are evolutionarily conserved. Strikingly, insertion of a human chromosome into mouse revealed that promoter-associated CGIs are refractory to DNA methylation regardless of host species, demonstrating that DNA sequence plays a central role in specifying the hypomethylated state through evolutionarily conserved mechanisms. In contrast, elements distal to gene promoters exhibited more variable methylation between host species, uncovering a widespread dependence on nucleotide frequency and occupancy of DNA-binding transcription factors in shaping the DNA methylation landscape away from gene promoters. This was exemplified by young CpG rich lineage-restricted repeat sequences that evaded DNA methylation in the absence of co-evolved mechanisms targeting methylation to these sequences, and species specific DNA binding events that protected against DNA methylation in CpG poor regions. Finally, transplantation of mouse chromosomal fragments into the evolutionarily distant zebrafish uncovered the existence of a mechanistically conserved and DNA-encoded logic which shapes CGI formation across vertebrate species.
Wireless Energy Harvesting for Internet of Things

Internet of Things (IoT) is an emerging computing concept that describes a structure in which everyday physical objects, each provided with unique identifiers, are connected to the Internet without requiring human interaction. Long-term and self-sustainable operation are key components for realization of such a complex network, and entail energy-aware devices that are potentially capable of harvesting their required energy from ambient sources. Among different energy harvesting methods such as vibration, light and thermal energy extraction, wireless energy harvesting (WEH) has proven to be one of the most promising solutions by virtue of its simplicity, ease of implementation and availability. In this article, we present an overview of enabling technologies for efficient WEH, analyze the life-time of WEH-enabled IoT devices, and briefly study the future trends in the design of efficient WEH systems and research challenges that lie ahead.
Non-uniform source modeling for distributed video coding

We introduce a novel correlation model, called predictive Binary Symmetric Channel (BSC), for Distributed Source Coding (DSC). We then consider non-uniform binary sources and show that, for the predictive BSC model, the non-uniformity does not reduce the compression rate in asymmetric DSC. We assess the minimum achievable rate loss induced by a mismatch between the assumed and the true correlation models. We also propose an LDPC-based decoder adapted to both the classical (additive) BSC and the new (predictive) BSC correlation models. Finally, for Distributed Video Coding (DVC) application, we propose a criterion that allows us to switch between the two correlation models.
Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain

Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient’s self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient’s medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain.
Inflammation interrelates to APP in sIBM: IL-1β induces accumulation of β-amyloid

Sir, Dr Greenberg has unfortunately misinterpreted some of our data or looked at them rather narrowly. He raises the following four points with respect to our conclusions drawn from our results: 1. Dr Greenberg argues that immune cells produce amyloid precursor protein (APP) and suggests that a correlation between APP and inflammatory mediators would hence be expected. This is true and in line with our immunohistochemical analysis as shown in Fig. 2B (Schmidt et al. , 2008). Probably Dr Greenberg did not appreciate that Fig 2B clearly demonstrates that the majority of the staining signal of APP in sIBM derives from the muscle fibres while the contribution by immune cells is minimal. The production of APP by the muscle fibres themselves was further substantiated by our in vitro experiments with exposure of muscle cells to IL-1β and IFN-γ (Fig. 5A and B). 2. Dr Greenberg notes that after removing the outlier, there is a significant correlation between IL-1β and APP in PM. This is true, but we had already pointed …
Effect of Root Coverage on Oral Health Impact Profile (G49): A Pilot Study

Purpose. The aim of this prospective longitudinal clinical pilot study was the evaluation of the effect on the Oral Health Impact Profile (OHIP) and patient-centered results of the envelope technique for Connective Tissue Graft (CTG). Methods. Sixteen patients (11 females) 24 to 71 years of age (42.6 ± 11.1) received CTG that had been harvested from the palate and grafted using the envelope technique. Prior to and 3 months after surgery, all patients were examined clinically, completed the OHIP-G49 questionnaire, and were asked to judge the results of surgery. Results. Mean baseline recession depth of 2.5 ± 0.8 mm was reduced by 1.2 ± 0.9 mm (P < .001). Root coverage amounted to 48 ± 39%. In 5 of 16 defects complete root coverage was achieved. Pain at the donor site was more pronounced than at recipient site regarding prevalence (8/6; P = .007), intensity (2.1 ± 2.3/1.1 ± 1.9 [visual analogue scale]; P = .016), and duration (1.4 ± 2.3/0.8 ± 1.4 days; P = .042). Baseline OHIP (15.7 ± 12.1) was decreased by 3.6 ± 8.5 three months after surgery (P = .139). Thirteen patients (81%) would undergo CTG surgery for similar reasons again. Conclusions. Root coverage using CTG according to the envelope technique provided improvement of OHIP as early as 3 months after surgery. Over all, patients were reasonably satisfied with the surgical technique and its results.
The Unique and Combined Effects of Apathy and Depression on Cognition in Parkinson's Disease.

BACKGROUND Apathy and depression are associated with poor cognition in patients with Parkinson's disease (PD). However, the cognitive signature of each syndrome is not well understood. The cognitive consequences of having apathy or depression, versus apathy and depression, are also unclear. OBJECTIVE This study investigated the unique and combined effects of apathy and depression on cognition in PD patients. METHODS PD patients were identified from a clinical research database as having self-reported apathy (n = 21), depression (n = 11), or both (n = 43). PD patients without apathy or depression served as the Control group (n = 49). The groups were of similar age, education, disease severity, age of symptom onset, and medication status. A multivariate analysis of variance (MANOVA) compared the groups on 17 neuropsychological test scores in the domains of attention, motor and psychomotor speed, construction, language, episodic memory, and executive functioning. RESULTS There was a significant overall effect of group: F(18,276) = 2.12, p = 0.006, ηp2=0.12. Univariate analyses and planned contrasts revealed medium-sized effects distinguishing only the control group and the group with both apathy and depression (ηp2=0.06-0.12) on measures of verbal fluency and manual, processing, and psychomotor speed. CONCLUSIONS PD patients with apathy alone or depression alone did not perform worse than PD controls on neuropsychological tests. Patients with apathy and depression performed worse than controls, but only on speed-based measures. This suggests that apathy and depression are associated with the same or similar circuits as those of cognitive and motor speed.
Full-Duplex Regenerative Relaying and Energy-Efficiency Optimization Over Generalized Asymmetric Fading Channels

This paper is devoted to the end-to-end performance analysis, optimal power allocation (OPA), and energy-efficiency (EE) optimization of decode-and-forward (DF)-based full-duplex relaying (FDR) and half-duplex relaying (HDR) systems. Unlike existing analyses and works that assume simplified transmission over symmetric fading channels, we consider the more realistic case of asymmetric multipath fading and shadowing conditions. To this end, exact and asymptotic analytic expressions are first derived for the end-to-end outage probabilities (OPs) of the considered DF-FDR set ups. Based on these expressions, we then formulate the OPA and EE optimization problems under given end-to-end target OP and maximum total transmit power constraints. It is shown that OP in FDR systems is highly dependent upon the different fading parameters and that OPA provides substantial performance gains, particularly, when the relay self-interference (SI) level is strong. Finally, the FDR is shown to be more energy-efficient than its HDR counterpart, as energy savings beyond 50% are feasible even for moderate values of the SI levels, especially at larger link distances, under given total transmit power constraints and OP requirements.