Miracle-dz/UniFAR-FTUs huggingface dataset:
Membrane anchoring of heparan sulfate proteoglycans by phosphatidylinositol and kinetics of synthesis of peripheral and detergent-solubilized proteoglycans in Schwann cells

Previous studies have shown that Schwann cells synthesize both peripheral and integral hydrophobic cell surface heparan sulfate proteoglycans (HSPGs). The experiments reported here were undertaken to investigate the mode of attachment of these proteins to the cell surface and their potential interrelationship. The binding of the hydrophobic HSPGs to membranes appears to be via covalently linked phosphatidylinositol based on the observation that incubation of the detergent-solubilized protein with purified phosphatidylinositol- specific phospholipase C significantly reduces the ability of the HSPGs to associate with phospholipid vesicles in a reconstitution assay. The peripherally associated HSPGs were released from the cells by incubation in the presence of heparin (10 mg/ml), 10 mM phytic acid (inositol hexaphosphate), or 2 M NaCl. These treatments also solubilized basement membrane HSPGs synthesized by the Schwann cells. These data suggest that the peripheral HSPGs are bound to the surface by electrostatic interactions. The peripheral and hydrophobic HSPGs were identical in overall size, net charge, length of glycosaminoglycan chains, and patterns of N-sulfation. To determine whether the peripheral HSPGs were derived from the membrane-bound form by cleavage of the membrane anchor, we examined the kinetics of synthesis and degradation of the two forms of HSPGs. The results obtained indicated the existence of two pools of detergent-solubilized HSPG with fast (t1/2 = 6 h) and slow (t1/2 = 55 h) turnover kinetics. The data were consistent with a model in which the peripheral HSPGs were derived from the slowly turning over pool of detergent-solubilized HSPGs.
Shunting and hyperpolarizing GABAergic inhibition in the high‐potassium model of ictogenesis in the developing rat hippocampus

Ontogenesis of GABAergic signaling may play an important role in developmental changes in seizure susceptibility in the high‐potassium model of ictogenesis in vitro. The age‐dependent effects of [K+]o on the reversal potential of the GABA(A)‐mediated responses and membrane potential in hippocampal slices in vitro were compared with the effect of GABA(A)‐receptors antagonists and GABA(A) modulators on high‐potassium induced seizures in the CA3 pyramidal layer of rat hippocampus in vivo. GABA(A) responses were depolarizing at P8–12 and hyperpolarizing at P17–21. In P8–12 rats, GABA(A) responses switch their polarity from depolarizing to hyperpolarizing upon elevation of extracellular potassium. At ∼10 mM [K+]o, activation of GABA(A) receptors produced an isoelectric, purely shunting response characterized by no changes in the membrane potential but an increase in the membrane conductance. In P17–21 rats, the hyperpolarizing GABA(A) driving force progressively increased with elevation of [K+]o. In P8–12 rats in vivo, GABA(A)‐receptor antagonists did not affect the occurrence of ictal discharges induced by intrahippocampal injection of 10 mM [K+]o, but significantly increased seizure duration. Diazepam and isoguvacine completely prevented seizures induced by 10 mM [K+]o. In P17–21 rats, GABA(A)‐receptor antagonists strongly increased the occurrence of ictal activity induced both by 10 mM [K+]o. Taken together, these results suggest that anticonvulsive effects of GABA are because of the combination of shunting and hyperpolarizing actions of GABA. Although shunting GABA is already efficient in the young age group, a developmental increase in the hyperpolarizing GABA(A) driving force likely contributes to the increase in the GABAergic control of seizures upon maturation. © 2007 Wiley‐Liss, Inc.
Regulation of nitrogen fixation by Fe-S protein II in Azotobacter vinelandii.

1. Several low-potential electron carriers from different sources can be photoreduced by the system 3,10-dimethyl-5-deazaisoalloxazine/N-tris(hydroxymethyl)methylglycine. The carriers studied were flavodoxin, ferredoxin I and iron-sulfur protein II from Azotobacter vinelandii and the flavodoxins from Desulfovibrio vulgaris and Peptostreptococcus elsdenii. 2. Electron transport to A. vinelandii nitrogenase was studied, employing different preparations of the enzyme: a crude complex; a complex reconstituted from the 0.27 M and 0.38 M NaCl fractions after DEAE-cellulose chromatography; a complex reconstituted from the 0.27 M and 0.38 M NaCl fraction plus iron-sulfur protein II purified from the 0.15 M NaCl fraction. Of all photoreduced carriers tested, only flavodoxin hydroquinone from A. vinelandii catalyzes significant electron transport to these complexes. 3. The time course of oxidation of substrate-amounts of A. vinelandii flavodoxin hydroquinone by catalytic amounts of crude nitrogenase complex shows three characteristic phases: an initial lag phase (1), a phase with constant rate over a range of redox potentials (2) and a final phase with rapidly declining rate (3). It was shown that the Fe-S protein II is responsible for the lag phase; the potential where phase 2 changes into phase 3 is at a higher value in the presence of Fe-S protein II. Pre-reduction of the enzyme photochemically abolishes phase 1 and causes phase 2 to proceed at a higher rate. The rate in phase 2 can be enhanced also by lowering the ‘starting potential’ of the flavodoxin hydroquinone/semiquinone couple. 4. A. vinelandii flavodoxin shuttles between its hydroquinone and semiquinone forms during steady-state electron transfer. Over 90% of the reducing equivalents is recovered in ethylene formed from acetylene. The concentrations of flavodoxin hydroquinone to give half-maximum rate in the acetylene reduction assay is 3–6 μM. A scheme is proposed for the regulation of electron donation to nitrogenase.
Phase-Sensitive Optical Coherence Tomography for Dynamic Photothermal Detection And Imaging of Gold Nano-Rods in Scattering Media and Biological Tissue

Gold nanoparticles are particularly attractive agents in medical imaging and laser therapy due to their unique optical properties. This study seeks to propose and analyse solutions aimed at imaging the distribution of gold nanoparticles in scattering media and biological tissue using a photothermal modulation technique combined with phase sensitive Optical Coherence Tomography (OCT). In this thesis, a spectrometer based phase sensitive OCT system and a swept source based phase sensitive OCT system are developed separately to fulfil this goal. In each OCT system, a Ti:Sa laser beam is coaxially combined with the OCT probing beam. The photothermal detection of gold nano-rods in multiple layer of the sample is completed by fixing the combined beam on a single lateral position on the sample and modulating the frequency of the Ti:Sa beam to the sample. The photothermal imaging of gold nano-rods in multiple layers of the sample is achieved by raster scanning the combined beams over the sample, modulating the Ti:Sa beam to the sample and then generating high contrast en-face images displaying the phase values retrieved from the OCT signal. Using the recently developed Complex Master/Slave interferometry technique, en-face images can be acquired in real time. In this thesis, application of this technique to a swept source based OCT system is presented. A system is specifically developed to produce en-face phase images of multiple layers of the studied sample. By doing this, the phase sensitive function of the Complex Master/Slave interferometry technique is demonstrated for the first time.
Seamless image-based texture atlases using multi-band blending

In this paper, we propose a novel method for creating a high-quality texture atlas from a 3D model and a set of calibrated images. Our method focuses on avoiding visual artifacts such as color discontinuities, ghosting or blurring, which typically arise from photometric and geometric inaccuracies. We first compute a partition of mesh faces which realizes a good trade-off between visual detail and color continuity at patch boundaries: we efficiently obtain a close-to-optimal seam placement using graph cuts optimization. We then apply a pixel-wise color correction in the vicinity of patch boundaries with a principled 3D extension of multi-band image blending: we achieve faultless color continuity while avoiding ghosting artifacts. We demonstrate the effectiveness of our method on two real-world large-scale scenes.
Autoimmune stiff person syndrome and related myelopathies: Understanding of electrophysiological and immunological processes

Stiff person syndrome (SPS) is a disabling autoimmune central nervous system disorder characterized by progressive muscle rigidity and gait impairment with superimposed painful spasms that involve axial and limb musculature, triggered by heightened sensitivity to external stimuli. Impaired synaptic GABAergic inhibition resulting from intrathecal B‐cell–mediated clonal synthesis of autoantibodies against various presynaptic and synaptic proteins in the inhibitory neurons of the brain and spinal cord is believed to be an underlying pathogenic mechanism. SPS is most often idiopathic, but it can occur as a paraneoplastic condition. Despite evidence that anti‐GAD and related autoantibodies impair GABA synthesis, the exact pathogenic mechanism of SPS is not fully elucidated. The strong association with several MHC‐II alleles and improvement of symptoms with immune‐modulating therapies support an autoimmune etiology of SPS. In this review, we discuss the clinical spectrum, neurophysiological mechanisms, and therapeutic options, including a rationale for agents that modulate B‐cell function in SPS. Muscle Nerve, 2012
Small RNA functions in carbon metabolism and virulence of enteric pathogens

Enteric pathogens often cycle between virulent and saprophytic lifestyles. To endure these frequent changes in nutrient availability and composition bacteria possess an arsenal of regulatory and metabolic genes allowing rapid adaptation and high flexibility. While numerous proteins have been characterized with regard to metabolic control in pathogenic bacteria, small non-coding RNAs have emerged as additional regulators of metabolism. Recent advances in sequencing technology have vastly increased the number of candidate regulatory RNAs and several of them have been found to act at the interface of bacterial metabolism and virulence factor expression. Importantly, studying these riboregulators has not only provided insight into their metabolic control functions but also revealed new mechanisms of post-transcriptional gene control. This review will focus on the recent advances in this area of host-microbe interaction and discuss how regulatory small RNAs may help coordinate metabolism and virulence of enteric pathogens.
Toward Operational Compensation of Ionospheric Effects in SAR Interferograms: The Split-Spectrum Method

The differential ionospheric path delay is a major error source in L-band interferograms. It is superimposed to topography and ground deformation signals, hindering the measurement of geophysical processes. In this paper, we proceed toward the realization of an operational processor to compensate the ionospheric effects in interferograms. The processor should be robust and accurate to meet the scientific requirements for the measurement of geophysical processes, and it should be applicable on a global scale. An implementation of the split-spectrum method, which will be one element of the processor, is presented in detail, and its performance is analyzed. The method is based on the dispersive nature of the ionosphere and separates the ionospheric component of the interferometric phase from the nondispersive component related to topography, ground motion, and tropospheric path delay. We tested the method using various Advanced Land Observing Satellite Phased-Array type L-band synthetic aperture radar interferometric pairs with different characteristics: high to low coherence, moving and nonmoving terrains, with and without topography, and different ionosphere states. Ionospheric errors of almost 1 m have been corrected to a centimeter or a millimeter level. The results show how the method is able to systematically compensate the ionospheric phase in interferograms, with the expected accuracy, and can therefore be a valid element of the operational processor.
Biological Activities of Aqueous and Organic Extracts from Tropical Marine Sponges

We report on screening tests of 66 extracts obtained from 35 marine sponge species from the Caribbean Sea (Curaçao) and from eight species from the Great Barrier Reef (Lizard Island). Extracts were prepared in aqueous and organic solvents and were tested for hemolytic, hemagglutinating, antibacterial and anti-acetylcholinesterase (AChE) activities, as well as their ability to inhibit or activate cell protein phosphatase 1 (PP1). The most interesting activities were obtained from extracts of Ircinia felix, Pandaros acanthifolium, Topsentia ophiraphidites, Verongula rigida and Neofibularia nolitangere. Aqueous and organic extracts of I. felix and V. rigida showed strong antibacterial activity. Topsentia aqueous and some organic extracts were strongly hemolytic, as were all organic extracts from I. felix. The strongest hemolytic activity was observed in aqueous extracts from P. acanthifolium. Organic extracts of N. nolitangere and I. felix inhibited PP1. The aqueous extract from Myrmekioderma styx possessed the strongest hemagglutinating activity, whilst AChE inhibiting activity was found only in a few sponges and was generally weak, except in the methanolic extract of T. ophiraphidites.
Glacial Inception on Baffin Island: The Role of Insolation, Meteorology, and Topography

AbstractGeologic evidence suggests that the last glacial inception (115 kya) occurred within the mountains of Baffin Island. Global climate models (GCMs) have difficulty simulating this climate transition, likely because of their coarse horizontal resolution that smooths topography and necessitates the use of cumulus parameterizations. A regional configuration of the Weather Research and Forecasting (WRF) Model is used to simulate the small-scale topographic and cloud processes neglected by GCMs, and the sensitivity of the region to Milankovitch forcing, topography, and meteorology is tested. It is found that ice growth is possible with 115-kya insolation, realistic topography, and slightly colder-than-average meteorology, represented by specific years within the past three decades. The simulation with low GCM-like topography shows a negative surface mass balance, even with the relevant orbital parameter configuration, demonstrating the criticality of realistic topography. The downslope growth of the ice .
Parameter Estimation of Quantum Channels

The efficiency of parameter estimation of quantum channels is studied in this paper. We introduce the concept of programmable parameters to the theory of estimation. It is found that programmable parameters obey the standard quantum limit strictly; hence, no speedup is possible in its estimation. We also construct a class of nonunitary quantum channels whose parameter can be estimated in a way that the standard quantum limit is broken. The study of estimation of general quantum channels also enables an investigation of the effect of noises on quantum estimation.
A Hydraulic Approach to Equilibria of Resource Selection Games

Drawing intuition from a (physical) hydraulic system, we present a novel framework, constructively showing the existence of a strong Nash equilibrium in resource selection games (i.e., asymmetric singleton congestion games) with nonatomic players, the coincidence of strong equilibria and Nash equilibria in such games, and the uniqueness of the cost of each given resource across all Nash equilibria. Our proofs allow for explicit calculation of Nash equilibrium and for explicit and direct calculation of the resulting (unique) costs of resources, and do not hinge on any fixed-point theorem, on the Minimax theorem or any equivalent result, on linear programming, or on the existence of a potential (though our analysis does provide powerful insights into the potential, via a natural concrete physical interpretation). A generalization of resource selection games, called resource selection games with I.D. -dependent weighting, is defined, and the results are extended to this family, showing the existence of strong equilibria, and showing that while resource costs are no longer unique across Nash equilibria in games of this family, they are nonetheless unique across all strong Nash equilibria, drawing a novel fundamental connection between group deviation and I.D. -congestion. A natural application of the resulting machinery to a large class of constraint-satisfaction problems is also described.
Species detection using environmental DNA from water samples

The assessment of species distribution is a first critical phase of biodiversity studies and is necessary to many disciplines such as biogeography, conservation biology and ecology. However, several species are difficult to detect, especially during particular time periods or developmental stages, potentially biasing study outcomes. Here we present a novel approach, based on the limited persistence of DNA in the environment, to detect the presence of a species in fresh water. We used specific primers that amplify short mitochondrial DNA sequences to track the presence of a frog (Rana catesbeiana) in controlled environments and natural wetlands. A multi-sampling approach allowed for species detection in all environments where it was present, even at low densities. The reliability of the results was demonstrated by the identification of amplified DNA fragments, using traditional sequencing and parallel pyrosequencing techniques. As the environment can retain the molecular imprint of inhabiting species, our approach allows the reliable detection of secretive organisms in wetlands without direct observation. Combined with massive sequencing and the development of DNA barcodes that enable species identification, this approach opens new perspectives for the assessment of current biodiversity from environmental samples.
Generation of Fgfr3 Conditional Knockout Mice

Fibroblast growth factor receptor 3 (FGFR3), highly conserved in both humans and murine, is one of key tyrosine kinase receptors for FGF. FGFR3 is expressed in different tissues, including cartilage, brain, kidney, and intestine at different development stages. Conventional knockout of Fgfr3 alleles leads to short life span, and overgrowth of bone. In clinic, human FGFR3 mutations are responsible for three different types of chondrodysplasia syndromes including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). For better understanding of the roles of FGFR3 in different tissues at different stages of development and in pathological conditions, we generated Fgfr3 conditional knockout mice in which loxp sites flank exons 9-10 in the Fgfr3 allele. We also demonstrated that Cre-mediated recombination using Col2a1-Cre, a Cre line expressed in chondrocyte during bone development, results in specific deletion of the gene in tissues containing cartilage. This animal model will be useful to study distinct roles of FGFR3 in different tissues at different ages.
Is unhealthy substance use associated with failure to receive cancer screening and flu vaccination? A retrospective cross-sectional study

Objective To compare cancer screening and flu vaccination among persons with and without unhealthy substance use. Design The authors analysed data from 4804 women eligible for mammograms, 4414 eligible for Papanicolou (Pap) smears, 7008 persons eligible for colorectal cancer (CRC) screening and 7017 persons eligible for flu vaccination. All patients were screened for unhealthy substance use. The main outcome was completion of cancer screening and flu vaccination. Results Among the 9995 patients eligible for one or more of the preventive services of interest, 10% screened positive for unhealthy substance use. Compared with women without unhealthy substance use, women with unhealthy substance use received mammograms less frequently (75.4% vs 83.8%; p<0.0001), but Pap smears no less frequently (77.9% vs 78.1%). Persons with unhealthy substance use received CRC screening no less frequently (61.7% vs 63.4%), yet received flu vaccination less frequently (44.7% vs 50.4%; p=0.01). In multivariable analyses, women with unhealthy substance use were less likely to receive mammograms (adjusted odds ratio 0.68; 95% CI 0.52 to 0.89), and persons with unhealthy substance use were less likely to receive flu vaccination (adjusted odds ratio 0.81; 95% CI 0.67 to 0.97). Conclusions Unhealthy substance use is a risk factor for not receiving all appropriate preventive health services.
Prevalence of thyroid microsomal and thyroglobulin autoantibodies in goitrous lesions.

BACKGROUND This prospective study was done to evaluate the serum levels of Microsomal and Thyroglobulin autoantibodies in patients with toxic diffuse goiter and nodular goitre (non-toxic) undergoing radio-iodine therapy and thyroidectomy respectively. METHODS Forty eight patients suffering from thyroid disorders, 29 with nodular goiter and 19 with toxic diffuse goitre (TDG) and 15 age & sex-matched normal controls were studied. Thyroid microsomal (MSAb) and thyroglobulin autoantibodies (TGAb) were estimated in the sera of all the subjects using the commercially available kits based on tanned red cell haemaglutination technique. RESULTS MSAb seropositivity in TDG and nodular goitre was found to be 78.9% and 51.7% respectively. On the other hand, TGAb seropositivity was 57.9% and 27.6% in cases of TDG and nodular goitre. 13.3% and 6.7% of the normal controls were positive for MSAb and TGAb respectively. CONCLUSION These findings indicate that autoimmunity is implicated in the genesis of commonly occurring thyroid disorders.
The Anti-tumour Agent, Cisplatin, and its Clinically Ineffective Isomer, Transplatin, Produce Unique Gene Expression Profiles in Human Cells

Cisplatin is a DNA-damaging anti-cancer agent that is widely used to treat a range of tumour types. Despite its clinical success, cisplatin treatment is still associated with a number of dose-limiting toxic side effects. The purpose of this study was to clarify the molecular events that are important in the anti-tumour activity of cisplatin, using gene expression profiling techniques. Currently, our incomplete understanding of this drug's mechanism of action hinders the development of more efficient and less harmful cisplatin-based chemotherapeutics. In this study the effect of cisplatin on gene expression in human foreskin fibroblasts has been investigated using human 19K oligonucleotide microarrays. In addition its clinically inactive isomer, transplatin, was also tested. Dual-fluor microarray experiments comparing treated and untreated cells were performed in quadruplicate. Cisplatin treatment was shown to significantly up- or down-regulate a consistent subset of genes. Many of these genes responded similarly to treatment with transplatin, the therapeutically inactive isomer of cisplatin. However, a smaller proportion of these transcripts underwent differential expression changes in response to the two isomers. Some of these genes may constitute part of the DNA damage response induced by cisplatin that is critical for its anti-tumour activity. Ultimately, the identification of gene expression responses unique to clinically active compounds, like cisplatin, could thus greatly benefit the design and development of improved chemotherapeutics.