Miracle-dz/UniFAR-FTUs huggingface dataset:
Update of the Clinical Impact and Issues Surrounding Dofetilide (Tikosyn) Therapy

Dofetilide (Tikosyn) is an oral anti-arrhythmic medication approved by the Food and Drug Administration (FDA) in 1999 for the management of persistent atrial fibrillation and flutter. A cautionary statement describing the side effect profile, including life-threatening arrhythmias and conduction abnormalities as well as monitoring strategies, accompanied the drug’s approval. The dofetilide package insert contains a black box warning that addresses the special requirements for initiation of the drug and prescribing and dispensing privileges. 1 As part of the warning, the FDA required that a distribution and education program for prescribers be developed to minimize the risk of potentially life-threatening arrhythmia as a condition for approval of dofetilide in the United States. In response, Pfizer developed a risk-management program that: 1) restricts dofetilide initiation to hospitalized patients, 2) places restrictions on outpatient dispensing, 3) requires prescribing physicians, physician assistants, and nurse practitioners complete an educational program on dofetilide, and 4) directs that healthcare institutions establish detailed dosing and monitoring recommendations for the drug. Additional information on this program can be found at www.tikosyn. com. Dofetilide is available only to hospitals and prescribers who have received appropriate dofetilide dosing and treatment initiation education. Retail pharmacies must be enrolled in the TIPS’ (Tikosyn in Pharmacy System) program in order to stock and dispense dofetilide. The black box warning also states that healthcare facilities should provide continuous electrocardiographic (ECG) monitoring, creatinine clearance calculation, and have cardiac resuscitation capability during the first 3 days of initiation and re-initiation of dofetilide. Indications Dofetilide is indicated for the conversion to and maintenance of normal sinus rhythm in patients with persistent atrial fibrillation or atrial flutter. Dofetilide should be used only in highly symptomatic patients (eg, palpitations, chest pain, dyspnea, fatigue, lightheadedness, syncope, and heart failure exacerbation) because of the risk of life-threatening ventricular arrhythmias associated with its administration. Adequate ventricular rate control can be achieved by using such agents as � -blockers (eg, esmolol or metroprolol), calcium channel blockers (such as diltiazem or verapamil), or digoxin. Management of atrial fibrillation
Expression of the early nodulin, ENOD40, in soybean roots in response to various lipo-chitin signal molecules.

The lipo-chitin (LCO) nodulation signal (nod signal) purified from Bradyrhizobium japonicum induced nodule primordia on soybean (i.e. Glycine soja) roots. These primordia were characterized by a bifurcated vascular connection, cortical cell division, and the accumulation of mRNA of the early nodulin gene, ENOD40. A chemically synthesized LCO identical in structure to the Nod signal purified from B. japonicum cultures showed the same activity when inoculated on to soybean roots. Surprisingly, synthetic LCO or chitin pentamer, inactive in inducing root hair curling (HAD) or cortical cell division (NOI) in G. soja, induced the transient accumulation of ENOD40 mRNA. In roots inoculated with such LCO, ENOD40 mRNA was abundant at 40 h after inoculation but decreased to the background levels 6 days after inoculation. In contrast, nod signals active in inducing HAD and NOI induced high levels of ENOD40 accumulation at 40 h and 6 days after inoculation. In situ hybridization analysis showed that ENOD40 mRNA accumulated in the pericycle of the vascular bundle at 24 h after root inoculation with nod signal. At 6 days post-inoculation with nod signal, ENOD40 expression was seen in dividing subepidermal cortical cells. These results provide morphological and molecular evidence that nodule induction in soybean in response to purified or synthetic nod signal is similar, if not identical, to nodule formation induced by bacterial inoculation. Surprisingly, ENOD40 mRNA accumulation occurs in response to non-specific chitin signals. This suggests that, in the case of ENOD40, nodulation specificity is not determined at the level of initial gene expression.
A 250 MHz 5 W RISC microprocessor with on-chip L2 cache controller

This superscalar microprocessor is a 32b implementation of the PowerPC Architecture(TM) specification based on a micro-architecture designed for high performance and low power. Two instructions per cycle can be dispatched in this superscalar design. The processor includes dual 32kB 8-way instruction and data caches, a floating-point unit, two integer units, a branch unit, a load/store unit, and a system unit. An L2 tag and cache controller with a dedicated L2 bus interface are added to provide a low-cost L2 cache solution using commodity SRAMs for the data.
A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2

The target of rapamycin complex 2 (TORC2) pathway is evolutionarily conserved and regulates cellular energetics, growth and metabolism. Loss of function of the essential TORC2 subunit Rictor (RICT-1) in Caenorhabditis elegans results in slow developmental rate, reduced brood size, small body size, increased fat mass and truncated lifespan. We performed a rict-1 suppressor RNAi screen of genes encoding proteins that possess the phosphorylation sequence of the AGC family kinase SGK, a key downstream effector of TORC2. Only RNAi to dpy-21 suppressed rict-1 slow developmental rate. DPY-21 functions canonically in the ten-protein dosage compensation complex (DCC) to downregulate the expression of X-linked genes only in hermaphroditic worms. However, we find that dpy-21 functions outside of its canonical role, as RNAi to dpy-21 suppresses TORC2 mutant developmental delay in rict-1 males and hermaphrodites. RNAi to dpy-21 normalized brood size and fat storage phenotypes in rict-1 mutants, but failed to restore normal body size and normal lifespan. Further dissection of the DCC via RNAi revealed that other complex members phenocopy the dpy-21 suppression of rict-1, as did RNAi to the DCC effectors set-1 and set-4, which methylate histone 4 on lysine 20 (H4K20). TORC2/rict-1 animals show dysregulation of H4K20 mono- and tri-methyl silencing epigenetic marks, evidence of altered DCC, SET-1 and SET-4 activity. DPY-21 protein physically interacts with the protein kinase SGK-1, suggesting that TORC2 directly regulates the DCC. Together, the data suggest non-canonical, negative regulation of growth and reproduction by DPY-21 via DCC, SET-1 and SET-4 downstream of TORC2 in C. elegans.
The late Pleistocene early microlithic assemblages of southern Africa

Abstract Results of a review of the early microlithic assemblages of southern Africa are discussed. Particular attention is given to the recognition of two geographic provinces, defined in terms of raw material availability and flaking technology, and to the palaeoecological implications of site distribution. Explanations are offered for the technological transitions between the Middle and Later Stone Ages, and between the Robberg and Albany Industries of the southern Cape. A brief description is included of the late Pleistocene early microlithic assemblage from Sehonghong, Lesotho.
Communication-centric design for FMC based I/O system

This paper presents a communication-centric reconfigurable design for FPGA Mezzanine Card (FMC) based I/O system dedicated to several industrial application domains. The introduction of FMC I/O standard has given a new purpose for FPGAs to be used as a communication platform. In fact, FPGAs can be used for more than just computational purpose in order to improve the system performance. Taking into account the features offered by FPGAs and FMCs, such as runtime reconfiguration and modularity, we have redefined the role of these devices to be used as a generic communication-centric platform. A new modular, runtime reconfigurable, Intellectual Property (IP)-based communication system for industrial applications has been designed. The efficiency and the performances of our platform are illustrated through a real industrial use-cases designed using a computationally intensive application and several I/O bus standards.
Human Matrix Metalloprotease Activation by Insults of Bacterial Infection Involving Proteases and Free Radicals

We found that human matrix metalloproteases (MMPs) may be processed from their proenzyme forms (proMMP) to their active forms by two new and unique mechanisms: Firstly, by bacterial proteases such as Pseudomonas elastase and Vibrio cholerae protease, which cleave off the N-terminal autoinhibitory domain (so-called cysteine switch) from proMMPs. The second mechanism depends on free radical generation by activated polymorphonuclear leukocytes (PMNs). In this case, peroxynitrite (ONOO-) or nitrogen dioxide radical (.NO2), the reaction products of either superoxide (O2.-) or molecular oxygen (O2) and nitric oxide (.NO), are the key reactants. Both O2. - and . NO are generated by activated macrophages and PMNs as a result of immunologic responses involving various proinflammatory cytokines. NO2 or ONOO- seems to interact with a single cysteine residue in the propeptide autoinhibitory domain, or so-called cysteine switch of proMMPs, thus transforming proMMPs into their active conformation. Furthermore, reactive oxygen species are known to inactivate the alpha1-protease inhibitor (alpha1-PI), a potent neutrophil elastase inhibitor in plasma. In addition, we found that such radicals activate MMPs which degrade and inactivate alpha1-PI by proteolysis. Thus, the activation of MMPs, accompanied by the inactivation of alpha1-PI, will bring about enhanced proteolytic damage to the matrix tissues of the infected sites by both MMPs and elastase.
Zinc as a Gatekeeper of Immune Function

After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.
A Service-Based Mobile Tourist Advisor

This paper presents a service based mobile applicat ion that assists tourists traveling to a country. The application provides tourists with context-aware information adapted to their personalized requireme nts. Detecting the real needs of the tourist is based on context management which is a key element in our system ‐ Murshid. Advice to tourists is proposed after sensi ng the context and a fine analysis of its ingredients. Mur shid is designed as client-server architecture and it uses GPS based location to provide a visual aid using UAE ma p. Murshid is flexible, user-friendly, portable, and s dynamic information. The application offers a set o f services to tourists through their mobile handsets, namely: special event notification, sightseeing, we ather forecasting, currency exchange, language translatio n, and location bookmarking and sharing. Each of the services recommends tourism guidance according to t he user’s context that is constantly changing since we are dealing with nomadic users. The application utilize s different context information to adapt its function ality according to the surrounding environment. This information can be spatial, temporal, or related to the environment. The context model includes the user location, the user profile, the current date, event s related information, and user interaction. The paper presen ts the context model, the system architecture, the service s implemented and offered, and an evaluation of the m ain functionalities of the system. It describes also ho w the context is managed in order to adapt the system functionality to the changes that may occur in orde r to react accordingly at the right time, at the right p lace and for the right person.
What Drives Bird Vision? Bill Control and Predator Detection Overshadow Flight

Although flight is regarded as a key behavior of birds this review argues that the perceptual demands for its control are met within constraints set by the perceptual demands of two other key tasks: the control of bill (or feet) position, and the detection of food items/predators. Control of bill position, or of the feet when used in foraging, and timing of their arrival at a target, are based upon information derived from the optic flow-field in the binocular region that encompasses the bill. Flow-fields use information extracted from close to the bird using vision of relatively low spatial resolution. The detection of food items and predators is based upon information detected at a greater distance and depends upon regions in the retina with relatively high spatial resolution. The tasks of detecting predators and of placing the bill (or feet) accurately, make contradictory demands upon vision and these have resulted in trade-offs in the form of visual fields and in the topography of retinal regions in which spatial resolution is enhanced, indicated by foveas, areas, and high ganglion cell densities. The informational function of binocular vision in birds does not lie in binocularity per se (i.e., two eyes receiving slightly different information simultaneously about the same objects) but in the contralateral projection of the visual field of each eye. This ensures that each eye receives information from a symmetrically expanding optic flow-field centered close to the direction of the bill, and from this the crucial information of direction of travel and time-to-contact can be extracted, almost instantaneously. Interspecific comparisons of visual fields between closely related species have shown that small differences in foraging techniques can give rise to different perceptual challenges and these have resulted in differences in visual fields even within the same genus. This suggests that vision is subject to continuing and relatively rapid natural selection based upon individual differences in the structure of the optical system, retinal topography, and eye position in the skull. From a sensory ecology perspective a bird is best characterized as “a bill guided by an eye” and that control of flight is achieved within constraints on visual capacity dictated primarily by the demands of foraging and bill control.
A new large Arabic database for offline handwriting recognition

To evaluate the performances of handwriting recognition systems, it is necessary to compare them objectively on the same database. A few freely databases are available for Arabic handwriting recognition, for this reason we have developed a new database of Algerian village names to be available freely for research and academic use. Up to now the database contains 1,209 forms including 26,580 binary and greyscale images representing 886 Algerian village names, collected from 1,209 writers. We also describe a new character segmentation algorithm for offline handwritten Arabic words. This algorithm uses a set of fuzzy ART neural networks as classifiers and Zernike invariant moments as features. The proposed system was trained and tested for the first time using the new database. A height segmentation and recognition accuracy were reported.
On the Convergence and Correctness of Impulse-Based Dynamic Simulation 1

Impulse-based dynamic simulation using the iterative method results in relatively simple algorithms which are easy to implement. However, two important theoretical questions have so far still remained open: (1) In what situations does the iterative procedure converge or diverge, and how can divergence be avoided? (2) Does the impulse-based simulation converge towards the exact solution of the dynamics problem as the step size is reduced? We will completely answer both questions in this paper. First we simplify the argumentation in that we prove that for every multibody system there is a dynamically and kinematically equivalent point mass system. Hence, our results on point mass systems also apply to multibody simulations. Next we show how to replace the iterative procedures by solving systems of linear equations. We prove that the matrices of these equation systems are non-singular if redundant constraints are removed from the point mass system in question. We prove further that the solution generated by the impulse-based procedure converges towards the exact solution of the dynamics problem as the step size is reduced towards zero. The proof is based on a detailed comparison of the impulse-based integration expression and the Taylor series solution. It is well known that the latter converges to the exact solution of the dynamics problem if a Lipschitz condition is satisfied. Comparison with the standard numerics on the basis of Lagrange multipliers shows significant advantages for the impulse-based method because the latter is completely free of drift problems, and stabilizations in the sense of Baumgarte are unnecessary. Because of the existence of methods of higher order, we can finally conclude that the impulse-based method is superior to the method with Lagrange multipliers.
Anesthesia for functional neurosurgery: the role of dexmedetomidine

Purpose of review The purpose of this review is to summarize current approaches to the anesthetic management of functional neurosurgery and to describe the application of an α-2-adrenergic agonist dexmedetomidine in the anesthetic management of functional neurosurgical procedures. Recent findings Dexmedetomidine, an α-2-adrenergic agonist, causes a unique kind of sedation, acting on the subcortical areas, which resembles natural sleep without respiratory depression. Experimental data demonstrate both cerebral vasoconstriction and vasodilatation, depending on the model and dose studied. At the clinically relevant doses, dexmedetomidine decreases cerebral blood flow and cerebral metabolic rate of oxygen in healthy volunteers. Clinical experience of dexmedetomidine use in functional neurosurgery is limited to small case-series. Nevertheless, these reports indicate that use of dexmedetomidine does not interfere with electrophysiologic monitoring, thus allowing brain mapping during awake craniotomy and microelectrode recording during implantation of deep-brain stimulators. Summary Dexmedetomidine has been demonstrated to provide a successful sedation without impairment of electrophysiologic monitoring in functional neurosurgery. Prospective randomized studies are warranted to delineate an optimal regimen of dexmedetomidine sedation and any dose-related influence on neurophysiologic function.
Feature Ablation for Preposition Disambiguation

The development of classification models for preposition disambiguation involves the generation of thousands of features describing the context of the preposition. The best modeling technique, supportvector machines, produce weights for each feature, but these weights are difficult to interpret and use for determining the most important features. One technique that can aid in this identification is feature ablation, removing features and assessing the effect on classification performance. We build upon standard approaches for feature ablation, removing feature sets one at a time, performing upwards of 5000 iterations for each preposition. We describe our algorithm in detail, including the detailed results that are generated with each iterate. We examine these results, suggesting that intuitions about how to describe preposition behavior might not hold. In particular, factors other than the syntactic and semantic properties of the complement and the governor frequently emerge as important. In this paper, we describe an algorithm for feature ablation using support-vector machine (SVM) modeling. In section 1, we provide background for SVM modeling used in preposition disambiguation, particularly identifying the types of features that are used. In section 2, we describe the algorithm that drills down through word-finding features, syntactic and semantic characterization features, and combinations of the two types. We describe the criteria used to identify feature sets to be ablated and the measures that are generated. In section 3, we examine these results and measures and how they might be used in characterizing preposition behavior. In section 4, we interpret the results and discuss the need for further investigations to use the results to aid in describing preposition behavior. 1. Features Used in SVM Modeling for Preposition Disambiguation As described in Litkowski (2014) and Litkowski (2016), the Pattern Dictionary of English Prepositions (PDEP) has processed 81509 sentences in three corpora using a lemmatizer, part-of-speech tagger, and dependency parser (Tratz and Hovy, 2011). Using the parse results, in CoNLL-X format, features are extracted to describe the context of a specified preposition in each sentence. Each feature consists of three components, a word position relative to the prepositions, a syntactic or semantic characterization of the element at the word position, and a value for the feature, depending on the word position and the type of characterization. We describe these features in more detail below. PDEP includes three corpora, collectively called the TPP Corpora (Litkowski, 2013a). The first was all FrameNet sentences (57 prepositions, 26739 instances), not just those used in SemEval (24 prepositions, which were divided into training and test sets). The second was a set of 20 sentences drawn from the Oxford English Corpus (OEC) to exemplify each sense in ODE, notably providing instances for multiword prepositional phrases (7485 sentences). The third was a set of sentences from the written
Time-Slotted Round-Trip Carrier Synchronization

We consider the problem of synchronizing the carriers of two sources in a wireless communication system with one destination. Carrier synchronization has been considered recently in cooperative communication systems where the sources wish to pool their antenna resources and transmit as a "distributed beamformer". Based on the concept of round-trip carrier synchronization first described in [1], we propose a new time-slotted round-trip carrier synchronization system and describe its implementation in systems with single-path or multi- path channels. The performance of the time-slotted round-trip carrier synchronization system is investigated in terms of the phase offset at the destination and the expected beamforming time before resynchronization is required. Our results suggest that the synchronization overhead can be small with respect to the potential beamforming gains.