Miracle-dz/UniFAR-FTUs huggingface dataset:
The pigmented epithelium, a bright partner against photoreceptor degeneration

Abstract Sight depends on the intimate association between photoreceptors and pigment epithelial cells. The evolutionary origin of this cellular tandem can be traced back to the emergence of bilateral animals, at least 450 million years ago, as they define the minimal unit of the ancestral prototypic eye. Phototransduction is a demanding process from the energetic and homeostatic points of view, and not surprisingly photoreceptive cells are particularly susceptible to damage and degeneration. Here, we will examine the different ancillary roles that the pigmented cells play in the physiology and homeostasis of photoreceptors, linking each one of these processes to the most common hereditary retinal diseases. We will discuss the challenges and opportunities of recent therapeutic advances based on cell and gene replacement. The transition from animal models to clinical trials will be addressed for each one of the different therapeutic strategies with a special focus on those depending on retinal-pigmented epithelial cells. Finally, we will discuss the potential impact of combining CRISPR technologies with gene and cell therapy approaches, which – in the frame of the personalized medicine revolution – may constitute a leap forward in the treatment of retinal dystrophies.
Exploration of Semantic Spaces Obtained from Czech Corpora

This paper is focused on semantic relations between Czech words. Knowledge of these relations is crucial in many research fields such as information retrieval, machine translation or document clustering. We obtained these relations from newspaper articles. With the help of LSA, HAL and COALS algorithms, many semantic spaces were generated. Experiments were conducted on various settings of parameters and on different ways of corpus preprocessing. The preprocessing included lemmatization and an attempt to use only ”open class” words. The computed relations between words were evaluated using the Czech equivalent of the Rubenstein-Goodenough test. The results of our experiments can serve as the clue whether the algorithms (LSA, HAL and COALS) originally developed for English can be also used for Czech texts.
In Vivo Recruitment of XPC to UV-induced Cyclobutane Pyrimidine Dimers by the DDB2 Gene Product*

The initial step in mammalian nucleotide excision repair (NER) of the major UV-induced photoproducts, cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4PPs), requires lesion recognition. It is believed that the heterodimeric proteins XPC/hHR23B and UV-DDB (UV-damaged DNA binding factor, composed of the p48 and p127 subunits) perform this function in genomic DNA, but their requirement and lesion specificity in vivo remains unknown. Using repair-deficient xeroderma pigmentosum (XP)-A cells that stably express photoproduct-specific photolyases, we determined the binding characteristics of p48 and XPC to either CPDs or 6–4PPs in vivo. p48 localized to UV-irradiated sites that contained either CPDs or 6–4PPs. However, XPC localized only to UV-irradiated sites that contained 6–4PPs, suggesting that XPC does not efficiently recognize CPDs in vivo. XPC did localize to CPDs when p48 was overexpressed in the same cell, signifying that p48 activates the recruitment of XPC to CPDs and may be the initial recognition factor in the NER pathway.
Parallel data cubes on multi-core processors with multiple disks

On-line Analytical Processing (OLAP) has become one of the most powerful and prominent technologies for knowledge discovery in VLDB (Very Large Database) environments. Central to the OLAP paradigm is the data cube, a multi-dimensional hierarchy of aggregate values that provides a rich analytical model for decision support. Various sequential algorithms for the efficient generation of the data cube have appeared in the literature. However, given the size of contemporary data warehousing repositories, multi-processor solutions are crucial for the massive computational demands of current and future OLAP systems. In this paper we discuss the development of MCMD-CUBE, a new parallel data cube construction method for multi-core processors with multiple disks. We present experimental results for a Sandy Bridge multi-core processor with four parallel disks. Our experiments indicate that MCMD-CUBE achieves very close to linear speedup. A critical part of our MCMD-CUBE method is parallel sorting. We developed a new parallel sorting method termed MCMD-SORT for multi-core processors with multiple disks which significantly outperforms the best previous method (PMSTXXL).
Metabolic Activation of the Anti-Hepatitis C Virus Nucleotide Prodrug PSI-352938

ABSTRACT PSI-352938 is a novel cyclic phosphate prodrug of β-d-2′-deoxy-2′-α-fluoro-2′-β-C-methylguanosine-5′-monophosphate with potent anti-HCV activity. In order to inhibit the NS5B RNA-dependent RNA polymerase, PSI-352938 must be metabolized to the active triphosphate form, PSI-352666. During in vitro incubations with PSI-352938, significantly larger amounts of PSI-352666 were formed in primary hepatocytes than in clone A hepatitis C virus (HCV) replicon cells. Metabolism and biochemical assays were performed to define the molecular mechanism of PSI-352938 activation. The first step, removal of the isopropyl group on the 3′,5′-cyclic phosphate moiety, was found to be cytochrome P450 (CYP) 3A4 dependent, with other CYP isoforms unable to catalyze the reaction. The second step, opening of the cyclic phosphate ring, was catalyzed by phosphodiesterases (PDEs) 2A1, 5A, 9A, and 11A4, all known to be expressed in the liver. The role of these enzymes in the activation of PSI-352938 was confirmed in primary human hepatocytes, where prodrug activation was reduced by inhibitors of CYP3A4 and PDEs. The third step, removal of the O6-ethyl group on the nucleobase, was shown to be catalyzed by adenosine deaminase-like protein 1. The resulting monophosphate was consecutively phosphorylated to the diphosphate and to the triphosphate PSI-352666 by guanylate kinase 1 and nucleoside diphosphate kinase, respectively. In addition, formation of nucleoside metabolites was observed in primary hepatocytes, and ecto-5′-nucleotidase was able to dephosphorylate the monophosphate metabolites. Since CYP3A4 is highly expressed in the liver, the CYP3A4-dependent metabolism of PSI-352938 makes it an effective liver-targeted prodrug, in part accounting for the potent antiviral activity observed clinically.
One-Dimensional Thermomechanical Constitutive Relations for Shape Memory Materials

The use of the thermoelastic martensitic transformation and its reverse transformation has recently been proposed and demonstrated for several active control ap plications. However, the present constitutive models have lacked several important funda mental concepts that are essential for many of the proposed intelligent material system ap plications such as shape memory hybrid composites. A complete, unified, one-dimensional constitutive model of shape memory materials is developed and presented in this paper. The thermomechanical model formulation herein will investigate important material characteristics involved with the internal phase transformation of shape memory alloys. These characteristics include energy dissipation in the material that governs the damping behavior, stress-strain-temperature relations for pseudoelasticity, and the shape memory effect. Some numerical examples using the model are also presented.
DRUG ACTION IN GALVANOTROPIC RESPONSES

Under strychninization involving reversal of reciprocal inhibition of the circular and longitudinal muscles, planarians and earthworms show reversed, i.e., anodal, galvanotropic responses, which neither nicotine nor atropine induce (in planarians). The results strengthen the conclusion (Crozier, 1926–27) that in causing reversal of inhibition strychnine acts primarily on central synapses or on homologous elements. Like other arthropods, on the other hand, Asellus is little affected by strychnine; no reversal occurs. Caffeine and atropine are even less effective. Nicotine evokes abnormal posture and movements, perhaps reversed, but no alteration of anodal galvanotropism.
Geometric algorithms for trap design

Geometric algorithms have successfully been applied to solve or give insight into problems in robotic manipulation. In this paper, we present a framework to filter polygonal parts on a track. The filter consists of a polygonal hole in the track; we refer to the filters as trap’s. For an n-sided polygonal part and an m-sided polygonal trap, we give an O((nm.(n + m))‘+‘) algorithm to. decide whether the part in a specific orientation will safely move across the trap or will fall through the trap and thus be filtered out. Furthermore, we show how to design various parameterized traps, ranging from simple gaps to arbitrary polygons which will filter out all but one of the different stable orientations of a given part.
A Study of Periodic and Aperiodic Ferromagnetic Antidot Lattices

OF DISSERTATION A STUDY OF PERIODIC AND APERIODIC FERROMAGNETIC ANTIDOT LATTICES This thesis reports our study of the effect of domain wall pinning by ferromagnetic (FM) metamaterials [1] in the form of periodic antidot lattices (ADL) on spin wave spectra in the reversible regime. This study was then extended to artificial quasicrystals in the form of Penrose P2 tilings (P2T). Our DC magnetization study of these metamaterials showed reproducible and temperature dependent knee anomalies in the hysteretic regime that are due to the isolated switching of the FM segments. Our dumbbell model analysis [2] of simulated magnetization maps indicates that FM switching in P2T is nonstochastic. We have also acquired the first direct, two-dimensional images of the magnetization of Permalloy films patterned into P2T using scanning electron microscopy with polarization analysis (SEMPA). Our SEMPA images demonstrate P2T behave as geometrically frustrated networks of narrow ferromagnetic film segments having near-uniform, bipolar (Ising-like) magnetization, similar to artificial spin ices (ASI). We find the unique aperiodic translational symmetry and diverse vertex coordination of multiply-connected P2T induce a more complex spin-ice behavior driven by exchange interactions in vertex domain walls, which differs markedly from the behavior of disconnected ASI governed only by dipolar interactions.
Leveraging "choice" to automate authorization hook placement

When servers manage resources on behalf of multiple, mutually-distrusting clients, they must mediate access to those resources to ensure that each client request complies with an authorization policy. This goal is typically achieved by placing authorization hooks at appropriate locations in server code. The goal of authorization hook placement is to completely mediate all security-sensitive operations on shared resources. To date, authorization hook placement in code bases, such as the X server and postgresql, has largely been a manual procedure, driven by informal analysis of server code and discussions on developer forums. Often, there is a lack of consensus about basic concepts, such as whatconstitutes a security-sensitive operation. In this paper, we propose an automated hook placement approach that is motivated by a novel observation --- that the deliberate choices made by clients for objects from server collections and for processing those objects must all be authorized. We have built a tool that uses this observation to statically analyze the server source. Using real-world examples (the X server and postgresql), we show that the hooks placed by our method are just as effective as hooks that were manually placed over the course of years while greatly reducing the burden on programmers.
Série Scientifique Scientific Series the Impact of Human Resources Practices on It Personnel Commitment, Citizenship Behaviors and Turnover Intentions the Impact of Human Resources Practices on It Personnel Commitment, Citizenship Behaviors and Turnover Intentions *

Reproduction partielle permise avec citation du document source, incluant la notice ©. Short sections may be quoted without explicit permission, provided that full credit, including © notice, is given to the source. Ce document est publié dans l'intention de rendre accessibles les résultats préliminaires de la recherche effectuée au CIRANO, afin de susciter des échanges et des suggestions. Les idées et les opinions émises sont sous l'unique responsabilité des auteurs, et ne représentent pas nécessairement les positions du CIRANO ou de ses partenaires. This paper presents preliminary research carried out at CIRANO and aims at encouraging discussion and comment. The observations and viewpoints expressed are the sole responsibility of the authors. They do not necessarily represent positions of CIRANO or its partners. Résumé / Abstract De nature conceptuelle, cet article présente un modèle de recherche portant sur la rétention des spécialistes en informatique au Québec. Ce modèle, inspiré largement de la littérature en gestion des ressources humaines, en comportement organisationnel et en technologies de l'information, examine les diverses relations entre sept types de pratiques de ressources humaines, deux formes particulières de comportements discrétionnaires, deux dimensions de l'engagement organisationnel et les intentions de quitter des spécialistes en technologies de l'information. La méthodologie utilisée pour tester les différentes hypothèses sous-jacentes au modèle de recherche est brièvement décrite. En dernier lieu, les limites principales de l'étude ainsi que les implications pour les recherches futures sont mises en lumière. The past few years have been the most threatening period for enterprises that use, manage or deal in IT. The source of the tumult has been the demand, supply, recruitment and especially retention of IT professionals. Recent literature reveals that a heavy investment in the implementation of HR practices may contribute to organizational success, specifically by reducing the turnover of IT professionals. As of today, very few empirical studies have rigorously examined the influence of relevant HR practices on turnover intentions of IT people. This study offers to fill that gap by testing an integrated model of turnover intentions that addresses the unique nature of the IT profession.
Multi-layer perceptrons and probabilistic neural networks for phoneme recognition

Two artificial neural networks have been trained to recognise phonemes in continuous speech: multi-layer perceptron (MLP) nets and probabilistic neural networks (PNN). The speech material was recorded by one male Swedish speaker and the sentences were phonetically labelled. Fifty sentences were used for training and another fifty were used for testing. Both networks had a single hidden layer and 38 output nodes corresponding to Swedish phonemes. The MLP was trained by the supervised backpropagation algorithm. The PNN was trained by a selforganising clustering algorithm, a stochastic approximation to the expectation maximisation algorithm. The classification results for a feed-forward MLP and the PNN were rather similar, but an MLP with simple recurrency using context nodes gave the best performance. Several other differences of practical value was noted.
Segmentation and interpolation of optic nerves in MR images

The measurement of human optic nerve is a difficult task because of its small structure. The goal of this work is to find the most suitable segmentation and interpolation models for the optic nerves in MR images, in order to improve the precision in the optic nerves area measurement. In this study, we have chosen Level Set Method (LSM) segmentation and Contrast-Guided (CG) interpolation models. We use the integrated LSM-CG model to produce distinct circular edge for the optic nerves prior the area measurement. It was found that the mean area of the optic nerve is 13.07 ± 1.29 mm2 from original images, and 12.20 ± 1.01 mm2 from the LSM-CG processed images, which are within the range of the reported literature values. These measurement were obtained from Proton Density (PD) images from five healthy volunteers on both 1.5T and 3.0T MRI scanners. The integrated LSM-CG model is suitable for processing optic nerve images to achieve higher resolution edges and allow more accurate area measurement.
An Improved Integer Frequency Offset Estimator using the P1 Symbol for OFDM System

This paper suggests an improved integer frequency offset (IFO) estimation scheme using P1 symbol for orthogonal frequency division multiplexing (OFDM) based the second generation terrestrial digital video broadcasting (DVB-T2) system. Proposed IFO estimator is designed by a low-complexity blind IFO estimation scheme, which is implemented with complex additions. Also, we propose active carriers (ACs) selection scheme in order to prevent performance degradation in blind IFO estimation. The simulation results show that under the AWGN and TU6 channels, the proposed method has low complexity than conventional method and almost similar performance in comparison with the conventional method. Keywords—OFDM, DVB-T2, P1 symbol, ACs, IFO.
An Intact Centrosome Is Required for the Maintenance of Polarization during Directional Cell Migration

Background Establishing and maintaining polarization is critical during cell migration. It is known that the centrosome contains numerous proteins whose roles of organizing the microtubule network range include nucleation, stabilization and severing. It is not known whether the centrosome is necessary to maintain polarization. Due to its role as the microtubule organizing center, we hypothesize that the centrosome is necessary to maintain polarization in a migrating cell. Although there have been implications of its role in cell migration, there is no direct study of the centrosome's role in maintaining polarization. In this study we ablate the centrosome by intracellular laser irradiation to understand the role of the centrosome in two vastly different cell types, human osteosarcoma (U2OS) and rat kangaroo kidney epithelial cells (PtK). The PtK cell line has been extensively used as a model for cytoskeletal dynamics during cell migration. The U2OS cell line serves as a model for a complex, single migrating cell. Methodology/Principal Findings In this study we use femtosecond near-infrared laser irradiation to remove the centrosome in migrating U2OS and PtK2 cells. Immunofluorescence staining for centrosomal markers verified successful irradiation with 94% success. A loss of cell polarization is observed between 30 and 90 minutes following removal of the centrosome. Changes in cell shape are correlated with modifications in microtubule and actin organization. Changes in cell morphology and microtubule organization were quantified revealing significant depolarization resulting from centrosome irradiation. Conclusions/Significance This study demonstrates that the centrosome is necessary for the maintenance of polarization during directed cell migration in two widely different cell types. Removal of the centrosome from a polarized cell results in the reorganization of the microtubule network into a symmetric non-polarized phenotype. These results demonstrate that the centrosome plays a critical role in the maintenance of cytoskeletal asymmetry during cell migration.
Overlay Consolidation of ISP-Provided Preferences

There is growing evidence that mutually beneficial outcomes can be achieved when content distribution overlays and their underlying ISPs collaborate through open interfaces. We further contribute to this body of work by considering consolidated topology construction strategies that integrate the information provided by multiple ISPs. We focus on situations with potentially conflicting, asymmetric preference costs, since these situations are expected to benefit more from the tradeoffs provided by consolidation to produce an overlay topology with desirable global properties. In this paper we develop a generic model for the multi-domain consolidation of ISP preferences expressed as costs for pairwise peer connections, where peers are grouped into clusters based on topology criteria. Using this model, we propose two consolidated topology construction strategies: Shared Cost, designed to provide a tradeoff for preference cost asymmetries, and Low Cost, designed to reduce the overall preference cost that the overlay imposes on all its underlying ISPs. We evaluate these two models through extensive simulations over a wide range of ISP and peer cluster sizes, and we show that preference consolidation can provide ISPs with outcomes more aligned with their preferences than those provided by non-consolidated operation.
A Temporal Reasoning based Social Calendar Framework

Electronic calendar has been intensively used in people’s life and work. In recent years it is popularized in the context of social networks, which forced the emergence of social calendar. For social calendar people is not just satisfied with creating, storing and exchanging their schedule data, they wants to use the calendar as a social network app, send invitations on some scheduled events, flexibly define the access rules on their scheduling, and even create event agenda in team manner. This paper describes a framework to answer those requirements. Using the standard interoperaterable calendar data format - iCalendar as calendar representation, the framework compiles the event information into an internal network structure, and incorporates a MapReduce consistency algorithm - that makes the framework suitable for large scale data processing in social network context.
Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling

Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one‐third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer‐associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti‐fatigue, anti‐ageing, and anti‐Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery.