Regulatory T cells in melanoma revisited by a computational clustering of FOXP3+ T cell subpopulations

CD4+ T cells that express the transcription factor FOXP3 (FOXP3+ T cells) are commonly regarded as immunosuppressive regulatory T cells (Treg). FOXP3+ T cells are reported to be increased in tumour-bearing patients or animals, and considered to suppress anti-tumour immunity, but the evidence is often contradictory. In addition, accumulating evidence indicates that FOXP3 is induced by antigenic stimulation, and that some non-Treg FOXP3+ T cells, especially memory-phenotype FOXP3low cells, produce proinflammatory cytokines. Accordingly, the subclassification of FOXP3+ T cells is fundamental for revealing the significance of FOXP3+ T cells in tumour immunity, but the arbitrariness and complexity of manual gating have complicated the issue. Here we report a computational method to automatically identify and classify FOXP3+ T cells into subsets using clustering algorithms. By analysing flow cytometric data of melanoma patients, the proposed method showed that the FOXP3+ subpopulation that had relatively high FOXP3, CD45RO, and CD25 expressions was increased in melanoma patients, whereas manual gating did not produce significant results on the FOXP3+ subpopulations. Interestingly, the computationally-identified FOXP3+ subpopulation included not only classical FOXP3high Treg but also memory-phenotype FOXP3low cells by manual gating. Furthermore, the proposed method successfully analysed an independent dataset, showing that the same FOXP3+ subpopulation was increased in melanoma patients, validating the method. Collectively, the proposed method successfully captured an important feature of melanoma without relying on the existing criteria of FOXP3+ T cells, revealing a hidden association between the T cell profile and melanoma, and providing new insights into FOXP3+ T cells and Treg

Cellulose Nanofiber Composite Membranes for Water Purification

Global water demand continues to increase because of population growth, urbanization, and climate change. Since there are limited natural water resources, water purification systems play a critical societal role. Membrane technologies are used widely to improve water quality for beneficial use. Therefore, the development of new membranes is an active area of research in the water purification field

Cellulose Nanofiber Composite Membranes for Water Purification

Global water demand continues to increase because of population growth, urbanization, and climate change. Since there are limited natural water resources, water purification systems play a critical societal role. Membrane technologies are used widely to improve water quality for beneficial use. Therefore, high-performance, nanofiber-based ion-exchange membranes were prepared for removal of heavy metals from impaired waters. Our hypothesis was that such membranes would have high metal ion capacities resulting from large surface area-to-volume ratios and high water permeability relative to barrier-type membranes such as reverse osmosis and nanofiltration. The nanofiber membranes were produced by electrospinning cellulose acetate nanofiber mats, which were strengthened by thermal-mechanical annealing and then converted to regenerated cellulose nanofiber mats. Subsequent surface modification transformed the membranes into ion-exchange membranes for removal of trace metal ions in water. The regenerated cellulose nanofiber mats were modified by grafting poly(itaconic acid) (dicarboxylic acid side groups) and poly(acrylic acid) (monocarboxylic acid side groups) to the surfaces of individual nanofibers. Direct-flow filtration measurements showed that the nanofiber membranes have water permeabilities much higher than reverse osmosis or nanofiltration membranes. Results of metal ion static and dynamic ion-exchange capacities will be presented and compared to more traditional ion-exchange media

Membrane Surface Modification

Processes for preparation of macroporous membranes having unusually high equilibrium protein binding capacities are described. Membranes include a self-supporting porous membrane substrate and a grafted polymeric film on the pore surfaces of the substrate. A polymeric film may be grafted to the porous membrane substrate using surface-initiated polymerization. The grafted polymer chains within the polymeric film can act as molecular `brushes` or `tentacles` in solution and can contain one or more capture chemistries for biomolecules. Membranes can be used in the separation and purification of biomolecules such as proteins, nucleic acids, virus or virus-like particles, endotoxins, and the like

Charge transfer electrostatic model of compositional order in perovskite alloys

We introduce an electrostatic model including charge transfer, which is shown to account for the observed B-site ordering in Pb-based perovskite alloys. The model allows charge transfer between A-sites and is a generalization of Bellaiche and Vanderbilt's purely electrostatic model. The large covalency of Pb^{2+} compared to Ba^{2+} is modeled by an environment dependent effective A-site charge. Monte Carlo simulations of this model successfully reproduce the long range compositional order of both Pb-based and Ba-based complex A(BB^{'}B^{''})O_3 perovskite alloys. The models are also extended to study systems with A-site and B-site doping, such as (Na_{1/2}La_{1/2})(Mg_{1/3}Nb_{2/3})O_3, (Ba_{1-x}La_{x})(Mg_{(1+x)/3}Nb_{(2-x)/3})O_3 and (Pb_{1-x}La_{x})(Mg_{(1+x)/3}Ta_{(2-x)/3})O_3. General trends are reproduced by purely electrostatic interactions, and charge transfer effects indicate that local structural relaxations can tip the balance between different B-site orderings in Pb based materials.Comment: 15 pages, 6 figure

The Rotation of Sub-Populations in omega Centauri

We present the first result of the Ital-FLAMES survey of red giant branch (RGB) stars in omega Cen. Radial velocities with a precision of ~0.5 km/s are presented for 650 members of omega Cen observed with FLAMES-Giraffe at the Very Large Telescope. We found that stars belonging to the metal -poor (RGB-MP), metal-intemediate (RGB-MInt) and metal-rich (RGB-a) sub -populations of Omega Cen are all compatible with having the same rotational pattern. Our results appear to contradict past findings by Norris et al., who could not detect any rotational signature for metal -rich stars. The slightly higher precision of the present measurements and the much larger sample size, especially for the metal-richer stars, appear as the most likely explanation for this discrepancy. The result presented here weakens the body of evidence in favour of a merger event in the past history of omega Cen.Comment: 5 pages, 3 fiures, electronic table can be obtained from E. Pancino. Accepted for publication in ApJ Letter

Sex-Specific Gait Patterns of Older Adults with Knee Osteoarthritis: Results from the Baltimore Longitudinal Study of Aging

Men and women exhibit different gait patterns during customary walking and may respond differently to joint diseases. The present paper aims to identify gait patterns associated with knee-OA separately in men and women. Participants included 144 men and 124 women aged 60 years and older enrolled in the Baltimore Longitudinal Study of Aging (BLSA) who underwent gait testing at a self-selected speed. Both men and women with knee-OA had lower ankle propulsion mechanical work expenditure (MWE; P < .001 for both) and higher hip generative MWE (P < .001) compared to non-OA controls. Women with knee-OA had a higher BMI (P = .008), slower gait speed (P = .049), and higher knee frontal-plane absorbing MWE (P = .007) than women without knee-OA. These differences were not observed in men. Understanding sex-specific differences in gait adaptation to knee-OA may inform the development of appropriate strategies for early detection and intervention for knee-OA in men and women

New insights (and new interrogations) in perinatal arterial ischemic stroke

With an incidence of 1/2800 to 1/5000 live-births, perinatal arterial ischemic stroke is the most frequent form of cerebral infarction in children. About 40% of the children do not have specific symptoms in the neonatal period, and are only recognized later with the emergence of motor impairment, developmental delay, specific cognitive deficiency or seizures. In the remaining 60%, children present with early symptoms, mostly recurrent focal seizures in the first 3 days of life. The diagnosis is easily confirmed by cranial ultrasounds and MRI. Early MRI has both a key role in the diagnosis, dating the injury, but also an important prognostic value to predict the motor outcome of the child. Indeed, although the infarct does not recur, the majority of children show subsequent sequels: cerebral palsy, epilepsy, cognitive or behavioural problems. Finding predictors of outcome regarding these latter concerns (and the way to prevent or alleviate them) is of major interest.The main etiological hypothesis for perinatal AIS is a cerebral embolus, originating from the placenta through the foramen ovale. Most of the established risk factors are indeed either determinants or biomarkers of vasculo-placental pathology. Injury to the cervico-cerebral arteries, giving rise to thrombus/embolus during the birthing process is also suggested. Both placento-embolic and traumatic theories are supported by a few, but well-analysed pathological or arteriographic reports. Nevertheless, their relative frequency, the implication of other mechanisms, and their repercussions to evidence-based preventive strategies remain to be determined. Moreover, the mechanism of stroke in the different groups of newborns with stroke (term vs. preterm; symptomatic neonates vs. those with a delayed presentation) is likely to be different, and there is a need for future studies to assess all populations as different entities. Neonatal supportive care remains important for all infants while there is no evidence for preventive anticoagulant use at present. In an effort to reduce neurological dysfunction, and in adjunction with ongoing physical therapy and pharmacological treatment, new rehabilitative interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used

Alternative Sample Loading Preparation for Thermal Ionization Mass Spectrometry

This contribution describes a new sample loading method for Thermal Ionization Mass Spectrometry (TIMS), which is used in nuclear safeguards and non-proliferation efforts worldwide and is known as the “gold standard” in isotopic ratio measurements of plutonium. TIMS analysis is used to determine grades of nuclear material and the extent of enrichment at production sites. The current sample loading method for TIMS analysis is known as “bead-loading”. While it provides the lowest detection limit of any known method for plutonium analysis, bead-loading is a difficult, time consuming, and expensive method that results in up to 20% sample loss. The major encumbrance of the method is the need to manually place a small polymer bead (~40 μm diameter) containing the plutonium sample onto a narrow and fragile ionization filament. We have developed an alternative sample loading method that eliminates the difficult and time-consuming steps by pre-coating the ionization filaments with a thin polymer film. Sample loading times have been reduced from hours to minutes. The films remain stably anchored to the filament, thus preventing sample loss. Ongoing TIMS measurements are testing our hypothesis that the method will increase overall measurement efficiency/sensitivity by isolating the sample in close proximity to the filament

Synthesising, using, and correcting for telluric features in high-resolution astronomical spectra

We present a technique to synthesise telluric absorption and emission features both for in-situ wavelength calibration and for their removal from astronomical spectra. While the presented technique is applicable for a wide variety of optical and infrared spectra, we concentrate in this paper on selected high-resolution near-infrared spectra obtained with the CRIRES spectrograph to demonstrate its performance and limitation. We find that synthetic spectra reproduce telluric absorption features to about 2%, even close to saturated line cores. Thus, synthetic telluric spectra could be used to replace the observation of telluric standard stars, saving valuable observing time. This technique also provides a precise in-situ wavelength calibration, especially useful for high-resolution near-infrared spectra in the absence of other calibration sources.Comment: 11 pages, 11 figures, accepted for publication in A&A (updated version