Miracle-dz/UniFAR-FTUs huggingface dataset:
Secondary lymphomas of the central nervous system: risk, prophylaxis and treatment

The recurrence of non-Hodgkin lymphoma (NHL) in the central nervous system (CNS) is rapidly fatal in most cases. Highly aggressive lymphomas, such as lymphoblastic and Burkitt lymphomas, carry a high risk of CNS relapse. CNS relapse in intermediately aggressive subtypes, such as diffuse large B-cell lymphoma, is uncommon, but not rare. The risk of CNS relapse in indolent lymphomas is low. Prognostic markers of CNS relapse include elevated serum lactate dehydrogenase levels, the presence of B symptoms, and extranodal involvement at more than one site. Most centers give prophylactic CNS chemotherapy to patients considered at high risk of CNS recurrence. However, definitions of risk factors vary, and there is a lack of consensus regarding prophylaxis indications. More research is needed to define which patients might benefit from CNS prophylaxis at initial treatment and to find the optimal regimen for prophylaxis. A variety of treatments have been used to treat CNS relapse, but current regimens have had little success in extending survival after CNS relapse. Although long-term survival has been reported in a minority of patients with isolated CNS recurrence after treatment with methotrexate, more effective regimens are needed if survival times after relapse are to be prolonged.
Effects of eccentrically and concentrically biased training on mouse muscle phenotype.

INTRODUCTION The molecular adaptations specifically induced by different muscle contraction types have only been partially elucidated. We previously demonstrated that eccentric contractions in human quadriceps elicited proteome modifications that suggest a muscle fiber typology adaptation. We address this question in a more systematic way by examining here the effects of different running modes on the mouse muscle proteome and the muscle fiber typology. METHODS Male adult mice (C57BL6) were randomly divided into downhill running (DHR) (quadricipital eccentrically biased contractions), uphill running (UHR) (quadricipital concentrically biased contractions), and untrained control (CONT) groups. Running groups performed five training sessions on an inclined treadmill for 75 to 135 min · d(-1), and the quadriceps muscles were dissected 96 h after the last session. Muscle protein extracts of DHR and UHR groups (n = 4/group) were subjected to a two-dimensional difference in gel electrophoresis (2D-DIGE) analysis coupled with mass spectrometry. The assessment of fiber type, size, and number was performed on the rectus femoris of the three groups (n = 6/group) using myosin heavy chain immunohistochemistry. RESULTS In the proteomic analysis, eight spots identified as the fast myosin heavy chain isoforms exhibited a lower abundance in DHR compared with UHR (P < 0.05, t-test). In contrast, adenosine triphosphate (ATP) synthase subunit α and tubulin β were more expressed in DHR (P < 0.05). A significant higher proportion of Type I and IIa fibers was found for DHR compared with UHR or CONT groups (P < 0.05, one-way ANOVA). CONCLUSIONS Our data suggest that the eccentrically biased contractions in mice induced specific adaptations in protein expression and muscle fiber composition, which may reflect a more oxidative muscle phenotype. The differences in stress placed on the muscle between both trainings may be responsible for some unique adaptations resulting from the eccentrically biased training.
Liberté et responsabilité des universités: Comment le contrôle de gestion participe à la construction d'un système de pilotage de la performance ?

Based on an analysis of the implementation of a formal management control system (MCS) in the French higher education sector, this article outlines the elements which contribute to the structuration of a global and organisational performance management system (PMS). Employing a conceptual framework originating in sociological neo-institutional theory, our longitudinal field study enables us to outline complex multi-level structuration mechanisms, involving interactions of a cognitive, political and normative nature, leading at this stage to different forms of PMS appropriation still not stabilized.
All gadget and no representation makes Jack a dull environment

In an Intelligent Environment, the user and the environment work together in a unique manner; the user expresses what he wishes to do, and the environment recognizes his intentions and helps out however it can. If well-implemented, such an environment allows the user to interact with it in the manner that is most natural for him personally. He should need virtually no time to learn to use it and should be more productive once he has. But to implement a useful and natural Intelligent Environment, the designers are faced with a daunting task: they must design a software system that senses what its users do, understands their intentions, and then responds appropriately. In this paper we argue that, in order to function reasonably in any of these ways, an Intelligent Environment must make use of declarative representations of what the user might do. We present our evidence in the context of the Intelligent Classroom, a facility that aids a speaker in this way and uses its understanding to produce a video of his presentation.
Fast DTT: a near linear algorithm for decomposing a tensor into factor tensors

As tensors provide a natural representation for the higher-order relations, tensor factorization techniques such as Tucker decomposition and CANDECOMP/PARAFAC decomposition have been applied to many fields. Tucker decomposition has strong capacity of expression, but the time complexity is unpractical for the large-scale real problems. On the other hand, CANDECOMP/PARAFAC decomposition is linear in the feature dimensionality, but the assumption is so strong that it abandons some important information. Besides, both of TD and CP decompose a tensor into several factor matrices. However, the factor matrices are not natural for the representation of the higher-order relations. To overcome these problems, we propose a near linear tensor factorization approach, which decompose a tensor into factor tensors in order to model the higher-order relations, without loss of important information. In addition, to reduce the time complexity and the number of the parameters, we decompose each slice of the factor tensors into two smaller matrices. We conduct experiments on both synthetic datasets and real datasets. The experimental results on the synthetic datasets validate that our model has strong capacity of expression. The results on the real datasets show that our approach outperforms the state-of-the-art tensor factorization methods.
Error performance analysis of cooperative spatial modulation with amplify-and-forward relaying

In this work, bit error rate analysis of amplify-and-forward cooperative spatial modulation (SM) systems with multiple antennas at relay and destination is investigated. Most of the studies in the literature of cooperative SM systems deal with the space shift keying (SSK), which is a special case of SM, and consider the single receive antenna at relay and destination. As it is known, the error performance of SM improves with increasing number of receive antennas, thus, the investigation of multi-antenna systems is essential. It is shown that the computer simulation results and theoretical results are in close match. On the other hand, cooperative SM with amplify-and-forward (AF) relaying provides 4 and 8 dB signal to noise ratio (SNR) gain for R=3 and R=4 bits/s/Hz spectral efficiency and Nr = 2 receive antenna number, respectively, compared to conventional M-ary cooperative modulated systems.
A Target Cell-Specific Role for Presynaptic Fmr1 in Regulating Glutamate Release onto Neocortical Fast-Spiking Inhibitory Neurons

In the mouse model of Fragile X syndrome, the Fmr1 knock-out, local excitation of layer 4 fast-spiking (FS) inhibitory neurons is robustly decreased by 50%, but the mechanisms mediating this change are unknown. Here, we performed recordings in acutely prepared slices obtained from Fmr1 “mosaic” mice, where Fmr1 is deleted in about half of all neurons, and we found that loss of presynaptic, but not postsynaptic, Fmr1 fully recapitulates the deficit. The change in connection strength is primarily due to a decrease in release probability indicating that FMRP normally positively regulates these processes. This change in presynaptic neurotransmitter release is observed both in the mosaic mice and in the constitutive Fmr1 knock-out mice. Manipulations in release probability enabled both the mimic and rescue of the impaired function in this synaptic pathway. Loss of presynaptic Fmr1 has no effect on excitatory synapses onto excitatory neurons, indicating a target cell-specific function for presynaptic FMRP. Finally, we demonstrate that the excitation decrement onto FS neurons also exists in layer 5 of the Fmr1 knock-out, suggesting a widespread role for presynaptic Fmr1 in the excitation of inhibitory neurons. In summary, we identify a novel function for presynaptic FMRP in promoting presynaptic neurotransmitter release, and we show that loss of this function accounts for impaired excitation of neocortical FS inhibitory neurons. These changes may contribute to the cognitive dysfunction and circuit hyperexcitability associated with Fragile X syndrome, including patients with complete deletion of FMRP and those with mosaic expression of FMRP.
Bounded-distance soft decision decoding of binary product codes

A two-step sub-optimal algorithm for decoding binary product codes is discussed. This algorithm realizes at least half the minimum Euclidean distance of the code. The fundamental geometric properties associated with the algorithm are investigated, and bounds on the number of nearest neighbors are derived. This investigation also results with an improved algorithm which achieves the minimum effective error coefficient, the number of minimum-weight codewords in the product code.
SuperDRUG2: a one stop resource for approved/marketed drugs

Abstract Regular monitoring of drug regulatory agency web sites and similar resources for information on new drug approvals and changes to legal status of marketed drugs is impractical. It requires navigation through several resources to find complete information about a drug as none of the publicly accessible drug databases provide all features essential to complement in silico drug discovery. Here, we propose SuperDRUG2 (http://cheminfo.charite.de/superdrug2) as a comprehensive knowledge-base of approved and marketed drugs. We provide the largest collection of drugs (containing 4587 active pharmaceutical ingredients) which include small molecules, biological products and other drugs. The database is intended to serve as a one-stop resource providing data on: chemical structures, regulatory details, indications, drug targets, side-effects, physicochemical properties, pharmacokinetics and drug–drug interactions. We provide a 3D-superposition feature that facilitates estimation of the fit of a drug in the active site of a target with a known ligand bound to it. Apart from multiple other search options, we introduced pharmacokinetics simulation as a unique feature that allows users to visualise the ‘plasma concentration versus time’ profile for a given dose of drug with few other adjustable parameters to simulate the kinetics in a healthy individual and poor or extensive metabolisers.
Architecture modeling language based on UML2.0

Existing ADLs (architecture description languages) have an advantage of formally specifying the architecture of component-based systems. But ADLs have not come into extensive use in industries since ADL users should learn a distinct notation specific to architecture, and ADLs do not address all stakes of development process that is becoming diversified everyday. On the other hand, UML is a de facto standard general modeling language for software developments as UML provides a consistent notation and various supporting tools during the whole software development cycle. A number of researches on architecture modeling based on UML have been progressed. In particular, many research results have been introduced that specialize UML by its extension mechanism in order to explicitly represent core architecture concepts that UML does not fully support. UML2.0 embraces much more concepts that are important to architecture modeling than UML1.x. In this paper, we examine architecture modeling elements that can be represented in UML2.0 and discuss how to extend and specialize UML2.0 in order to make it more suitable for representing architectures.
Cloning, expression, and characterization of the human eosinophil eotaxin receptor

Although there is a mounting body of evidence that eosinophils are recruited to sites of allergic inflammation by a number of beta- chemokines, particularly eotaxin and RANTES, the receptor that mediates these actions has not been identified. We have now cloned a G protein- coupled receptor, CC CKR3, from human eosinophils which, when stably expressed in AML14.3D10 cells bound eotaxin, MCP-3 and RANTES with Kds of 0.1, 2.7 and 3.1 nM, respectively. CC CKR3 also bound MCP-1 with lower affinity, but did not bind MIP-1 alpha or MIP-1 beta. Eotaxin, RANTES, and to a lessor extent MCP-3, but not the other chemokines, activated CC CKR3 as determined by their ability to stimulate a Ca(2+) - flux. Competition binding studies on primary eosinophils gave binding affinities for the different chemokines which were indistinguishable from those measured with CC CKR3. Since CC CKR3 is prominently expressed in eosinophils we conclude that CC CKR3 is the eosinophil eotaxin receptor. Eosinophils also express a much lower level of a second chemokine receptor, CC CKR1, which appears to be responsible for the effects of MIP-1 alpha.
IL-1 is a Master Regulator of Tissue and Islet Inflammation in Type 2 Diabetes

standing of the pathogenesis of Type 2 diabetes (3, 13, 34, 52). Over-nutrition and inactivity promote insulin resistance. To cope with this increased demand of insulin secretion, the pancreatic islet needs to enhance its secretory activity. In most individuals, such an adaptation does occur during early stages of increased metabolic stress (characterized by over-nutrition). Although successful adaptation of the -cell permits maintenance of normal metabolism throughout life in most subjects, this adaptation eventually fails in some individuals, depending on the genetically determined ability of the -cell to adapt and the severity of the resistance to insulin. The reasons for this failure to maintain sufficient insulin secretion are a combined decrease in -cell mass and defective insulin secretion. Several mechanisms have been proposed to explain this failure, including ER stress, oxidative stress, amyloid deposition, lipotoxicity, and glucotoxicity (28, 33, 51, 54, 65). Interestingly, all these factors may induce an inflammatory response, whereas some may be the result of the inflammation (16, 17, 19, 31). Initially, an inflammatory response is probably deployed to promote -cell repair and regeneration. However, as it becomes chronic, the situation gets complicated by, e.g., the activation of auto-inflammatory processes that may then become deleterious. Interestingly, similar auto-inflammatory processes occur in insulin-sensitive tissues. Therefore, Type 2 diabetes can be considered an auto-inflammatory disease. Consequently, it can be treated by agents blocking this vicious cycle such as IL-1 antagonists, or more downstream by NFB modulation via salsalate or similar compounds (15, 59). In this article, we will review the evidence for insulitis in Type 2 diabetes, the mechanisms inducing this inflammatory process, its physiological and pathological role, and the therapeutic consequences. Evidence for an Islet Inflammatory Process in -Cell Failure During Type 2 Diabetes
Conveying the 3D Shape of Smoothly Curving Transparent Surfaces via Texture

Transparency can be a useful device for depicting multiple overlapping surfaces in a single image. The challenge is to render the transparent surfaces in such a way that their 3D shape can be readily understood and their depth distance from underlying structures clearly perceived. This paper describes our investigations into the use of sparsely-distributed discrete, opaque texture as an artistic device for more explicitly indicating the relative depth of a transparent surface and for communicating the essential features of its 3D shape in an intuitively meaningful and minimally occluding way. The driving application for this work is the visualization of layered surfaces in radiation therapy treatment planning data, and the technique is illustrated on transparent isointensity surfaces of radiation dose. We describe the perceptual motivation and artistic inspiration for defining a stroke texture that is locally oriented in the direction of greatest normal curvature (and in which individual strokes are of a length proportional to the magnitude of the curvature in the direction they indicate), and we discuss two alternative methods for applying this texture to isointensity surfaces defined in a volume. We propose an experimental paradigm for objectively measuring observers' ability to judge the shape and depth of a layered transparent surface, in the course of a task which is relevant to the needs of radiotherapy treatment planning, and use this paradigm to evaluate the practical effectiveness of our approach through a controlled observer experiment based on images generated from actual clinical data.
Virtual Video Camera: Image‐Based Viewpoint Navigation Through Space and Time

We present an image‐based rendering system to viewpoint‐navigate through space and time of complex real‐world, dynamic scenes. Our approach accepts unsynchronized, uncalibrated multivideo footage as input. Inexpensive, consumer‐grade camcorders suffice to acquire arbitrary scenes, for example in the outdoors, without elaborate recording setup procedures, allowing also for hand‐held recordings. Instead of scene depth estimation, layer segmentation or 3D reconstruction, our approach is based on dense image correspondences, treating view interpolation uniformly in space and time: spatial viewpoint navigation, slow motion or freeze‐and‐rotate effects can all be created in the same way. Acquisition simplification, integration of moving cameras, generalization to difficult scenes and space–time symmetric interpolation amount to a widely applicable virtual video camera system.
A Policy-Based Framework for Automated SLA Negotiation for Internet-Based Virtual Computing Environment

Service Level Agreements (SLAs) play an important role in guaranteeing successful collaborations among autonomous entities in Internet-based Virtual Computing Environment (iVCE). However, traditional static and predefined SLAs are not suitable for the open and dynamic iVCE. This paper proposes a policy-based framework for supporting dynamic and automated SLA negotiations between autonomous entities in iVCE. Requirements or constraints on SLA attributes as well as negotiation strategies of negotiating parties are both specified in policy specifications using a simple but expressive policy language that extends the WS-Policy framework. According to these policies, a negotiation agent will be dynamically created for each negotiation party, which is responsible for SLA negotiations on behalf of its owner party. We have implemented a prototype of our framework and demonstrated our approach through a case study.
Single metallic nanoparticle imaging for protein detection in cells

We performed a visualization of membrane proteins labeled with 10-nm gold nanoparticles in cells, using an all-optical method based on photothermal interference contrast. The high sensitivity of the method and the stability of the signals allows 3D imaging of individual nanoparticles without the drawbacks of photobleaching and blinking inherent to fluorescent markers. A simple analytical model is derived to account for the measurements of the signal amplitude and the spatial resolution. The photothermal interference contrast method provides an efficient, reproducible, and promising way to visualize low amounts of proteins in cells by optical means.
Undertreatment of Urinary Incontinence in General Practice

BACKGROUND: In the urinary incontinence guidelines that are issued by the Dutch College of General Practitioners, treatment guidelines are related to the type of incontinence. It is unknown whether treatment of urinary incontinence in general practice complies with these guidelines. OBJECTIVE: To describe treatment patterns and costs of urinary incontinence. METHODS: The source population for this retrospective cohort study included all women aged ≥40 years in the Integrated Primary Care Information general practice research database. Women were included in the final study cohort if they were newly identified as being urinary incontinent during the study period (1998–2000) and had at least one year of follow-up after the first diagnosis/treatment. The type of incontinence, treatment course, and costs of incontinence were assessed during the first year after the subjects' identification. RESULTS: The final study cohort comprised 1663 women (mean age 68.5 y). Overall, 71% of newly identified women with urinary incontinence did not receive active treatment within one year after identification. In 13%, the first treatment was bladder training or pelvic floor exercises, and 11% started treatment with a bladder relaxant drug. First treatment was related to the type of incontinence; however, in <50% of the women, the type of incontinence was reported or could be assessed. Absorbent products were used by 66% of the women; 87% of them received no active treatment. The mean direct costs of urinary incontinence over the first year amounted to ¢392 per woman, of which ¢200 (51%) for absorbent products. CONCLUSIONS: Less than one-third of the women with newly identified urinary incontinence were actively treated for their incontinence. Although treatment patterns were in line with guidelines, the high rate of undertreatment points to the need for better patient and physician education.
Enhanced Methamphetamine Metabolism in Rhesus Macaque as Compared with Human: An Analysis Using a Novel Method of Liquid Chromatography with Tandem Mass Spectrometry, Kinetic Study, and Substrate Docking

Methamphetamine (MA), which remains one of the widely used drugs of abuse, is metabolized by the cytochrome P450 (P450) family of enzymes in humans. However, metabolism of methamphetamine in macaques is poorly understood. Therefore, we first developed and validated a very sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method using solid phase extraction of rhesus plasma with a lower limit of quantitation at 1.09 ng/ml for MA and its metabolites, 4-hydroxy methamphetamine (4-OH MA), amphetamine (AM), 4-OH amphetamine (4-OH AM), and norephedrine. We then analyzed plasma samples of MA-treated rhesus, which showed >10-fold higher concentrations of AM (∼29 ng/ml) and 4-OH AM (∼28 ng/ml) than MA (∼2 ng/ml). Because the plasma levels of MA metabolites in rhesus were much higher than in human samples, we examined MA metabolism in human and rhesus microsomes. Interestingly, the results showed that AM and 4-OH AM were formed more rapidly and that the catalytic efficiency (Vmax/Km) for the formation of AM was ∼8-fold higher in rhesus than in human microsomes. We further examined the differences in these kinetic characteristics using three selective inhibitors of each human CYP2D6 and CYP3A4 enzymes. The results showed that each of these inhibitors inhibited both d- and l-MA metabolism by 20%–60% in human microsomes but not in rhesus microsomes. The differences between human and rhesus CYP2D6 and CYP3A4 enzymes were further assessed by docking studies for both d and l-MA. In conclusion, our results demonstrated an enhanced MA metabolism in rhesus compared with humans, which is likely to be caused by differences in MA-metabolizing P450 enzymes between these species.