Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration

Purpose To determine whether gene polymorphisms of the major genetic risk factor for age-related macular susceptibility 2 (ARMS2 A69S) and the complement factor H Y402H influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration. Methods This prospective cohort study included 90 patients (90 eyes) with exudative age related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (Mitchell et al.). Injections were administered monthly when a patient lost five letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness (CSRT). Genotypes (rs10490924 and rs1061170) were analyzed using gene sequence analysis. Best-corrected visual acuity (BCVA) and CSRT values were compared between ARMS2 and complement factor H genotypes. Multiple regression analysis was used to assess the statistical significance. Results Mean increase in visual acuity was 4.44±8.12 letters with a 103.63±94.7 µm decrease in CSRT. BCVA improvement was statistically significant in all genotype groups except in homozygous 69S in the AMRS2 gene. CSRT and BCVA changes were correlated (r=0.2521; 95% CI: 0.04746–0.4364, p=0.0165). Multiple regression analysis revealed a significant impact of 69S (p=0.015) on the change in BCVA. Conclusions Visual acuity did not improve during the study in patients homozygous for ARMS2 69S, despite a decrease in CSRT. Further investigation is needed to confirm our findings and understand the mechanisms involved.
Cyclic GMP-dependent Protein Kinase Iα Inhibits Thrombin Receptor-mediated Calcium Mobilization in Vascular Smooth Muscle Cells*

Vascular smooth muscle contractile state is regulated by intracellular calcium levels. Nitric oxide causes vascular relaxation by stimulating production of cyclic GMP, which activates type I cGMP-dependent protein kinase (PKGI) in vascular smooth muscle cells (VSMC), inhibiting agonist-induced intracellular Ca2+ mobilization ([Ca2+]i). The relative roles of the two PKGI isozymes, PKGIα and PKGIβ, in cyclic GMP-mediated inhibition of [Ca2+]i in VSMCs are unclear. Here we have investigated the ability of PKGI isoforms to inhibit [Ca2+]i in response to VSMC activation. Stable Chinese hamster ovary cell lines expressing PKGIα or PKGIβ were created, and the ability of PKGI isoforms to inhibit [Ca2+]i in response to thrombin receptor stimulation was examined. In Chinese hamster ovary cells stably expressing PKGIα or PKGIβ, 8-Br-cGMP activation suppressed [Ca2+]i by thrombin receptor activation peptide (TRAP) by 98 ± 1 versus 42 ± 5%, respectively (p <0.002). Immunoblotting studies of cultured human VSMC cells from multiple sites using PKGIα- and PKGIβ-specific antibodies showed PKGIα is the predominant VSMC PKGI isoform. [Ca2+]i following thrombin receptor stimulation was examined in the absence or presence of cyclic GMP in human coronary VSMC cells (Co403). 8-Br-cGMP significantly inhibited TRAP-induced [Ca2+]i in Co403, causing a 4-fold increase in the EC50 for [Ca2+]i. In the absence of 8-Br-cGMP, suppression of PKGIα levels by RNA interference (RNAi) led to a significantly greater TRAP-stimulated rise in [Ca2+]i as compared with control RNAi-treated Co403 cells. In the presence of 8-Br-cGMP, the suppression of PKGIα expression by RNAi led to the complete loss of cGMP-mediated inhibition of [Ca2+]i. Adenoviral overexpression of PKGIβ in Co403 cells was unable to alter TRAP-stimulated Ca2+ mobilization either before or after suppression of PKGIα expression by RNAi. These results support that PKGIα is the principal cGMP-dependent protein kinase isoform mediating inhibition of VSMC activation by the nitric oxide/cyclic GMP pathway.
Use of type-specific antimyosins to demonstrate the transformation of individual fibers in chronically stimulated rabbit fast muscles

Continuous stimulation of a rabbit fast muscle at 10 Hz changes its physiological and biochemical parameters to those of a slow muscle. These transformations include the replacement of myosin of one type by myosin of another type. Two hypotheses could explain the cellular basis of these changes. First, if fibers were permanently programmed to be fast or slow, but not both, a change from one muscle type to another would involve atrophy of one fiber type accompanied by de novo appearance of the other type. Alternatively, preexisting muscle fibers could be changing from the expression of one set of genes to the expression of another. Fluorescein-labeled antibodies against fast (AF) and slow (AS) muscle myosins of rabbits have been prepared by procedures originally applied to chicken muscle. In the unstimulated fast peroneus longus muscle, most fibers stained only with AF; a small percentage stained only with AS; and no fibers stained with both antibodies. In stimulated muscles, most fibers stained with both AF and AS; with increasing time of stimulation, there was a progressive decrease in staining intensity with AF and a progressive increase in staining intensity with AS within the same fibers. These results are consistent with a theory that individual preexisting muscle fibers can actually switch from the synthesis of fast myosin to the synthesis of slow myosin.
The Dutch secret: how to provide safe drinking water without chlorine in the Netherlands

The Netherlands is one of the few countries where chlorine is not used at all, neither for primary disinfection nor to maintain a residual disinfectant in the distribution network. The Dutch approach that allows production and distribution of drinking water without the use of chlorine while not compromising microbial safety at the tap, can be summarized as follows: 1. Use the best source available, in order of preference: microbiologically safe groundwater, surface water with soil passage such as artificial recharge or bank filtration, direct treatment of surface water in a multiple barrier treatment; 2. Use a preferred physical process treatment such as sedimentation, filtration and UV-disinfection. If absolutely necessary, also oxidation by means of ozone or peroxide can be used, but chlorine is avoided; 3. Prevent ingress of contamination during distribution; 4. Prevent microbial growth in the distribution system by production and distribution of biologically stable (biostable) water and the use of biostable materials; 5. Monitor for timely detection of any failure of the system to prevent significant health consequences. OA-fund TU Delft
Empowering Business Students - Using Web 2.0 Tools in the Classroom

This paper discusses the design of a course to empower business students using Web 2.0 technologies. We explore the learning phenomenon as a way to bring forward a process of continuous improvement supported by social software. We develop a framework to assess the infrastructure against expectations of skill proficiency using Web 2.0 tools which must emerge as a result of registering in an introductory business information and communication technologies (ICT) course in a business school of a Canadian university. We use Friedman‟s (2007) thesis that the “world is flat” to discuss issues of globalization and the role of ICT. Students registered in the course are familiar with some of the tools we introduce and use in the course. The students are members of Facebook or MySpace, regularly check YouTube, and use Wikipedia in their studies. They use these tools to socialize. We broaden the students‟ horizons and explore the potential business benefits of such tools and empower the students to use Web 2.0 technologies within a business
Asynchronous blind signal decomposition using tiny-length code for Visible Light Communication-based indoor localization

Indoor localization is a fundamental capability for service robots and indoor applications on mobile devices. To realize that, the cost and performance are of great concern. In this paper, we introduce a lightweight signal encoding and decomposition method for a low-cost and low-power Visible Light Communication (VLC)-based indoor localization system. Firstly, a Gold-sequence-based tiny-length code selection method is introduced for light encoding. Then a correlation-based asynchronous blind light-signal decomposition method is developed for the decomposition of the lights mixed with modulated light sources. It is able to decompose the mixed light-signal package in real-time. The average decomposition time-cost for each frame is 20 ms. By using the decomposition results, the localization system achieves accuracy at 0.56 m. These features outperform other existing low-cost indoor localization approaches, such as WiFiSLAM.
A License Plate Super-resolution Reconstruction Algorithm Based on Manifold Learning

To address the problem of low resolution in surveillance video, which leads to difficulty in recognizing license plates, this paper presents a new license plate image super-resolution reconstruction method based on manifold learning. Firstly, the mapping between low-resolution images and high-resolution images in training set is obtained by learning method. Then image feature vectors are extracted by linear discriminant analysis (LDA) algorithm and its parameters are modeled by locally linear embedding (LLE) algorithm. Finally the high resolution image is reconstructed by the mapping relation. Experimental results show that the proposed algorithm has better effect on super-resolution restoration for real low-resolution plate image, significantly improve the license plate character identification.
Viewpoint distortion compensation in practical surveillance systems

Our aim is to estimate the perspective-effected geometric distortion of a scene from a video feed. In contrast to all previous work we wish to achieve this using from low-level, spatio-temporally local motion features used in commercial semi-automatic surveillance systems. We: (i) describe a dense algorithm which uses motion features to estimate the perspective distortion at each image locus and then polls all such local estimates to arrive at the globally best estimate, (ii) present an alternative coarse algorithm which subdivides the image frame into blocks, and uses motion features to derive block-specific motion characteristics and constrain the relationships between these characteristics, with the perspective estimate emerging as a result of a global optimization scheme, and (iii) report the results of an evaluation using nine large sets acquired using existing close-circuit television (CCTV) cameras. Our findings demonstrate that both of the proposed methods are successful, their accuracy matching that of human labelling using complete visual data.
Algorithm-based diskless checkpointing for fault tolerant matrix operations

The paper is an exploration of diskless checkpointing for distributed scientific computations. With the widespread use of the "network of workstations" (NOW) platform for distributed computing, long-running scientific computations need to tolerate the changing and often faulty nature of NOW environments. We present high-performance implementations of several algorithms for distributed scientific computing, including Cholesky factorization, LU factorization, QR factorization, and preconditioned conjugate gradient. These implementations are able to run on PVM networks of at least N processors, and can complete with low overhead as long as any N processors remain functional. We discuss the details of how the algorithms are tuned for fault-tolerance, and present the performance results on a PVM network of SUN workstations, and on the IBM SP2. <<ETX>>
Randomization does not reduce the average delay in parallel packet switches

Switching cells in parallel is a common approach to build switches with very high external line rate and a large number of ports. A prime example is the parallel packet switch (in short, PPS) in which a demultiplexing algorithm sends cells, arriving at rate R on N input-ports, through one of K intermediate slower switches, operating at rate r<R.This paper presents lower bounds on the average queuing delay introduced by the PPS relative to an optimal work-conserving FCFS switch, for demultiplexing algorithms that does not have full and immediate information about the switch status. The bounds hold even if the algorithm is randomized.These lower bounds are shown to be asymptotically optimal through a new methodology for analyzing the maximal relative queuing delay; this clearly upper bounds their average relative queuing delay. The methodology is used to devise a new algorithm that relies on slightly out-dated global information on the switch status. It is also used to provide, for the first time, a complete proof of the maximum relative queuing delay provided by the fractional traffic dispatch [19, 22] algorithm.
Candida albicans Biofilms Produce Antifungal-Tolerant Persister Cells

ABSTRACT Fungal pathogens form biofilms that are highly recalcitrant to antimicrobial therapy. The expression of multidrug resistance pumps in young biofilms has been linked to increased resistance to azoles, but this mechanism does not seem to underlie the resistance of mature biofilms that is a model of in vivo infection. The mechanism of drug resistance of mature biofilms remains largely unknown. We report that biofilms formed by the major human pathogen Candida albicans exhibited a strikingly biphasic killing pattern in response to two microbicidal agents, amphotericin B, a polyene antifungal, and chlorhexidine, an antiseptic, indicating that a subpopulation of highly tolerant cells, termed persisters, existed. The extent of killing with a combination of amphotericin B and chlorhexidine was similar to that observed with individually added antimicrobials. Thus, surviving persisters form a multidrug-tolerant subpopulation. Interestingly, surviving C. albicans persisters were detected only in biofilms and not in exponentially growing or stationary-phase planktonic populations. Reinoculation of cells that survived killing of the biofilm by amphotericin B produced a new biofilm with a new subpopulation of persisters. This suggests that C. albicans persisters are not mutants but phenotypic variants of the wild type. Using a stain for dead cells, rare dark cells were visible in a biofilm after amphotericin B treatment, and a bright and a dim population were physically sorted from this biofilm. Only the dim cells produced colonies, showing that this method allows the isolation of yeast persisters. Given that persisters formed only in biofilms, mutants defective in biofilm formation were examined for tolerance of amphotericin B. All of the known mutants affected in biofilm formation were able to produce normal levels of persisters. This finding indicates that attachment rather than formation of a complex biofilm architecture initiates persister formation. Bacteria produce multidrug-tolerant persister cells in both planktonic and biofilm populations, and it appears that yeasts and bacteria have evolved analogous strategies that assign the function of survival to a small part of the population. In bacteria, persisters are dormant cells. It remains to be seen whether attachment initiates dormancy that leads to the formation of fungal persisters. This study suggests that persisters may be largely responsible for the multidrug tolerance of fungal biofilms.
Single-conformation and diastereomer specific ultraviolet and infrared spectroscopy of model synthetic foldamers: alpha/beta-peptides.

Resonant two-photon ionization (R2PI), UV hole-burning (UVHB), and resonant ion-dip infrared (RIDIR) spectroscopies have been used to record single-conformation infrared and ultraviolet spectra of three model synthetic foldamers with heterogeneous backbones, alpha/beta-peptides Ac-beta(3)-hAla-L-Phe-NHMe (betaalphaL), Ac-beta(3)-hAla-D-Phe-NHMe (betaalphaD), and Ac-L-Phe-beta(3)-hAla-NHMe (alphabetaL), isolated and cooled in a supersonic expansion. BetaalphaL and betaalphaD are diastereomers, differing only in the configuration of the alpha-amino acid residue; betaalphaL and alphabetaL contain the same residues, but differ in residue order. In all three alpha/beta-peptides the beta(3)-residue has S absolute configuration. UVHB spectroscopy is used to determine that there are six conformers of each molecule and to locate and characterize their S(0)-S(1) transitions in the origin region. RIDIR spectra in the amide NH stretch region reflect the number and strength of intramolecular H-bonds present. Comparison of the RIDIR spectra with scaled, harmonic vibrational frequencies and infrared intensities leads to definite assignments for the conformational families involved. C8/C7(eq) double-ring structures are responsible for three conformers of betaalphaL and four of betaalphaD, including those with the most intense transitions in the R2PI spectra. This preference for C8/C7(eq) double rings appears to be dictated by the C7(eq) ring of the alpha-peptide subunit. Three of the conformers of betaalphaL and betaalphaD form diastereomeric pairs (A/A', C/C', and G/G') that have nearly identical S(0)-S(1) origin positions in the UV and belong to the same conformational family, indicating no significant change associated with the change in chirality of the alpha-peptide subunit. However, betaalphaL favors formation of a C6/C5 conformer over C11, while the reverse preference holds in betaalphaD. Calculations indicate that the selective stabilization of the lowest-energy C11(g(+)) structure in betaalphaD occurs because this structure minimizes steric effects between the beta(2) methylene group and C=O(1). In the alpha/beta-peptide alphabetaL, two conformers dominate the spectrum, one assigned to a C5/C8 bifurcated double-ring, and the other to a C5/C6 double-ring structure. This preference for C5 rings in the alpha/beta-peptide occurs because the C5 ring is further stabilized by an amide NH.pi interaction involving an NH group on the adjacent amide, as it is in the alpha-peptides. Comparison of the NH stretch spectra of C8/C7(eq) structures in betaalphaL with their C7(eq)/C8 counterparts in alphabetaL shows that the central amide NH stretch is shifted to lower frequency by some 50-70 cm(-1) due to cooperative effects associated with the central amide accepting and donating a H-bond to neighboring amide groups. This swaps the ordering of the C8 and C7 NH stretch fundamentals in the two molecules.
Functional ontologies for cognition: The systematic definition of structure and function

Cognitive scientists have traditionally specified the functional components of cognitive skills on the basis of behavioural studies of normal and neurologically impaired subjects. The results of functional imaging studies are challenging these classical models because there is a high degree of overlap among the neural systems activated by tasks that share no cognitive components. This suggests that a given neuronal structure can perform multiple functions that depend on the areas with which it interacts. However, there will be a limited range of functions that an area can perform given that its anatomical (intrinsic and extrinsic) connectivity is fixed. Assigning labels that encompass the operations that each area performs should enable a task to be re-described in terms of the functions of the areas activated. In other words, function should predict the structure and conversely structure should predict function. These systematic descriptions are referred to as ontologies. We argue that a systematic ontology for cognition would facilitate the integration of cognitive and anatomical models and organise the cognitive components of diverse tasks into a single framework. These points are illustrated with cognitive and anatomical models of reading and object recognition.
Recurrence of glioblastoma after radio-chemotherapy is associated with an angiogenic switch to the CXCL12-CXCR4 pathway

Angiogenesis is one of the key features of glioblastoma (GBM). Our objective was to explore the potential changes of angiogenic factors in GBM between initial diagnosis and recurrence after radiotherapy-temozolomide (RT/TMZ). Paired frozen tumors from both initial and recurrent surgery were available for 29 patients. Screening of genes expressions related to angiogenesis was performed using RT- PCR arrays on 10 first patients. Next, RNA expressions of the selected genes were analyzed on all samples. Protein expression was examined by immunohistochemistry. The anti-tumor effect of AMD3100 (anti-CXCR4) was tested in GBM explants. In the screening step, the initial-recurrence expression changes contributed to a selection of seven genes (VEGFA, VEGFR2, VEGFR1, CXCL12, CXCR4, uPA HIF1α). By quantitative RT-PCR, RNA expressions of CXCR4 (p = 0.029) and CXCL12 (p = 0.107) were increased while expressions of HIF1α (p = 0.009) and VEGFR2 (p = 0.081) were decreased at recurrence. Similarly, CXCL12 protein expression tended to increase (p = 0.096) while VEGFR2 staining was decreased (p = 0.004) at recurrence. An increase of anti-tumoral effect was observed with the combination of AMD3100 and RT/TMZ versus RT/TMZ alone in GB explants. Recurrence of GB after chemo-radiation could be associated with a switch of angiogenic pattern from VEGFR2-HIF1α to CXCL12-CXCR4 pathway, leading to new perspectives in angiogenic treatment
An approach to spacecraft anomaly detection problem using kernel feature space

Development of advanced anomaly detection and failure diagnosis technologies for spacecraft is a quite significant issue in the space industry, because the space environment is harsh, distant and uncertain. While several modern approaches based on qualitative reasoning, expert systems, and probabilistic reasoning have been developed recently for this purpose, any of them has a common difficulty in obtaining accurate and complete a priori knowledge on the space systems from human experts. A reasonable alternative to this conventional anomaly detection method is to reuse a vast amount of telemetry data which is multi-dimensional time-series continuously produced from a number of system components in the spacecraft.This paper proposes a novel "knowledge-free" anomaly detection method for spacecraft based on Kernel Feature Space and directional distribution, which constructs a system behavior model from the past normal telemetry data from a set of telemetry data in normal operation and monitors the current system status by checking incoming data with the model.In this method, we regard anomaly phenomena as unexpected changes of causal associations in the spacecraft system, and hypothesize that the significant causal associations inside the system will appear in the form of principal component directions in a high-dimensional non-linear feature space which is constructed by a kernel function and a set of data.We have confirmed the effectiveness of the proposed anomaly detection method by applying it to the telemetry data obtained from a simulator of an orbital transfer vehicle designed to make a rendezvous maneuver with the International Space Station.