Advanced Accelerator Magnets for Upgrading the LHC Bottura, L.; de Rijk, G.; Rossi, L. ...
IEEE transactions on applied superconductivity,
06/2012, Letnik:
22, Številka:
3
Journal Article, Conference Proceeding
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Odprti dostop
The Large Hadron Collider is working at about half its design value, limited by the defective splices of the magnet interconnections. While the full energy will be attained after the splice ...consolidation in 2014, CERN is preparing a plan for a Luminosity upgrade (High Luminosity LHC) around 2020 and has launched a pre-study for exploring an Energy upgrade (High Energy LHC) around 2030. Both upgrades strongly rely on advanced accelerator magnet technology, requiring dipoles and quadrupoles of accelerator quality and operating fields in the 11-13 T range for the luminosity upgrade and 16-20 T range for the energy upgrade. The paper will review the last ten year of Nb 3 Sn accelerator magnet R&D and compare it to the needs of the upgrades and will critically assess the results of the Nb 3 Sn and HTS technology and the planned R&D programs also based on the inputs of first year of LHC operation.
Altered control of T follicular helper (Tfh) cells can lead to generation of autoantibodies and autoimmune manifestations. Signaling pathways that selectively limit pathogenic responses without ...affecting the protective function of Tfh cells are unknown. Here we show that the ATP-gated ionotropic P2X7 receptor restricts the expansion of aberrant Tfh cells and the generation of self-reactive antibodies in experimental murine lupus, but its activity is dispensable for the expansion of antigen-specific Tfh cells during vaccination. P2X7 stimulation promotes caspase-mediated pyroptosis of Tfh cells and controls the development of pathogenic ICOS
IFN-γ-secreting cells. Circulating Tfh cells from patients with systemic lupus erythematosus (SLE) but not primary antiphospholipid syndrome (PAPS), a nonlupus systemic autoimmune disease, were hyporesponsive to P2X7 stimulation and resistant to P2X7-mediated inhibition of cytokine-driven expansion. These data point to the P2X7 receptor as a checkpoint regulator of Tfh cells; thus, restoring P2X7 activity in SLE patients could selectively limit the progressive amplification of pathogenic autoantibodies, which deteriorate patients' conditions.
The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. Nucleosome number in cells was ...considered fixed, but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker, and variant histones, and a correspondingly reduced number of nucleosomes, possibly because HMGB1 facilitates nucleosome assembly. Yeast nhp6 mutants lacking Nhp6a and -b proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and affects the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform and can be modelled assuming that different nucleosomal sites compete for available histones. Sites with a high propensity to occupation are almost always packaged into nucleosomes both in wild type and nucleosome-depleted cells; nucleosomes on sites with low propensity to occupation are disproportionately lost in nucleosome-depleted cells. We suggest that variation in nucleosome number, by affecting nucleosomal occupancy both genomewide and gene-specifically, constitutes a novel layer of epigenetic regulation.
The prevalence of obesity, an established risk factor for many chronic diseases, including several types of cancer, has risen steadily over the past four decades in the United States and worldwide. ...To date, research in this area has focused on the epidemiologic associations between obesity and cancer risk, as well as on the mechanisms underlying those associations. However, an emerging but understudied issue of clinical importance is the diminution of chemotherapeutic efficacy in obese cancer patients. The mechanisms underlying the negative impact of obesity on therapeutic responses are likely multifactorial. The effects of obesity on chemotherapy drug pharmacokinetics and dosage have been extensively reviewed elsewhere, so this review will focus on the interplay among obesity, increased inflammation, metabolic perturbations, and chemoresistance. The ultimate goal of this review is to delineate areas for future research that could lead to the identification of new targets and strategies for improved cancer outcomes in obese patients.
Clinical Pharmacology & Therapeutics (2014); 96 4, 458–463. doi:10.1038/clpt.2014.136
Despite a number of studies on hypnosis as analgesia and anesthesia in several medical conditions, case studies on patients with multiple chemical sensitivity (MCS) are still relatively few. This ...case study is about a female patient with MCS who underwent dental removal using hypnosis as the sole anesthesia. The paradigm in which we work is psychosocial genomics of clinical hypnosis. We used the mind-body transformations therapy, one of the clinical methods of the psychosocial genomics paradigm. In order to induce not only effective analgesia and anesthesia but also a condition of well-being, problem-solving, effective coping and self-empowerment in our patient, 3 different hypnotic protocols were used in a multidimensional approach. Although further research is needed, our work might open up new scenarios for the application of hypnosis as sole anesthesia in conditions such as MCS.
Background
Published treatment technique comparisons for postoperative left-sided whole breast irradiation (WBI) with deep-inspiration breath-hold (DIBH) are scarce, small, and inconclusive. In this ...study, fully automated multi-criterial plan optimization, generating a single high-quality, Pareto-optimal plan per patient and treatment technique, was used to compare for a large patient cohort 1) intensity modulated radiotherapy (IMRT) with two tangential fields and 2) volumetric modulated arc therapy (VMAT) with two small tangential subarcs.
Materials and methods
Forty-eight randomly selected patients recently treated with DIBH and 16 × 2.66 Gy were included. The optimizer was configured for the clinical planning protocol. Comparisons between IMRT and VMAT included dosimetric plan parameters, estimated excess relative risks (ERR) for toxicities, delivery times, MUs, and deliverability accuracy at a linac.
Results
The automatically generated IMRT and VMAT plans applied in this study were similar or higher in quality than the manually generated clinical plans. For equal PTVin V95% (98.4 ± 0.9%), VMAT had significant advantages compared to IMRT regarding breast dose homogeneity and doses in heart and ipsilateral lung, at the cost of some minor deteriorations for contralateral breast (few cases with larger deteriorations) and lung. Conformality improved from 1.38 to 1.18 (
p
< 0.001). With VMAT, ERR for major coronary events and ipsilateral lung tumors were reduced by 3% (range: −1–12%) and 16% (range: −3–38%), respectively. MUs and delivery times were higher for VMAT. There were no statistical differences in γ passing rates.
Conclusion
For WBI in conservative therapy of left-sided breast patients treated with DIBH, VMAT with two tangential subarcs was generally dosimetrically superior to IMRT with two tangential static fields. Results need confirmation by robustness analyses.
It has been shown that the synthesis of TiO2 nanotubes by anodization provides outstanding properties to Ti surfaces intended for dental and orthopedic implants applications. Beyond the very ...well-known potential of these surfaces to improve osseointegration and avoid infection, the knowledge on the adhesion and degradation behavior of TiO2 nanotubes under the simultaneous action of wear and corrosion is still poorly understood and these are issues of tremendous importance. The main aim of this work is to investigate, for the first time, the tribo-electrochemical degradation behavior of Ti surfaces decorated with TiO2 nanotubes before and after bio-functionalization treatments.
Well-aligned TiO2 nanotubes (NTs) were produced containing elements natively present in bone such as calcium (Ca) and phosphorous (P), in addition of zinc (Zn) as an antimicrobial agent and stimulator of bone formation. The synthesis of Ca/P/Zn-doped nanotubes (NT-Ca/P/Zn) was achieved by reverse polarization and anodization treatments applied to conventional TiO2 nanotubes grown by two-step anodization. The nanotube surfaces were analyzed by scanning electron microscopy (SEM) while dark-field scanning transmission electron microscopy (STEM-DF) was used to characterize the Ti/TiO2 nanotubular films interfaces. Tribo-electrochemical tests were conducted under reciprocating sliding conditions in artificial saliva. The open circuit potential (OCP) was monitored before, during and after sliding tests, and the coefficient of friction (COF) values were registered during rubbing action. The wear tracks resulting from sliding tests were characterized by SEM and wear volume measurements were carried out by 2D profilometry.
The results show that the tribo-electrochemical behavior of TiO2 nanotubes was significantly improved after bio-functionalization treatments. The higher electrochemical stability and lower mechanical degradation of these films was correlated with their improved adhesion strength to Ti substrate, which is granted by the nano-thick oxide film formed at the interface region, during bio-functionalization processes. A first insight on the degradation mechanisms taking place during tribo-electrochemical action is proposed. The outcomes of this study may contribute in a great extent for the development of new implant surfaces with improved biomechanical stability and thus contribute for the long term success of dental implants.
•Bone-inspired TiO2 nanotubes (NTs) were bio-functionalized with Ca, P and Zn.•Bio-functionalization granted better adhesion between TiO2 NTs and Ti substrate.•Bio-functionalized TiO2 nanotubes display improved tribo-electrochemical resistance.•Ca/P/Zn-doped NTs display an enhanced resistance to mechanical degradation.
Helminth infections, including hookworms and Schistosomes, can cause severe disability and death. Infection management and control would benefit from identification of biomarkers for early detection ...and prognosis. While animal models suggest that Trefoil Factor Family proteins (TFF2 and TFF3) and interleukin-33 (IL-33) -driven type 2 immune responses are critical mediators of tissue repair and worm clearance in the context of hookworm infection, very little is known about how they are modulated in the context of human helminth infection. We measured TFF2, TFF3, and IL-33 levels in serum from patients in Brazil infected with Hookworm and/or Schistosomes, and compared them to endemic and non-endemic controls. TFF2 was specifically elevated by Hookworm infection in females, not Schistosoma or co-infection. This elevation was correlated with age, but not worm burden. TFF3 was elevated by Schistosoma infection and found to be generally higher in females. IL-33 was not significantly altered by infection. To determine if this might apply more broadly to other species or regions, we measured TFFs and cytokine levels (IFNγ, TNFα, IL-33, IL-13, IL-1β, IL-17A, IL-22, and IL-10) in both the serum and urine of Nigerian school children infected with S. haematobium. We found that serum levels of TFF2 and 3 were reduced by infection, likely in an age dependent manner. In the serum, only IL-10 and IL-13 were significantly increased, while in urine IFN-γ, TNF-α, IL-13, IL-1β, IL-22, and IL-10 were significantly increased in by infection. Taken together, these data support a role for TFF proteins in human helminth infection.
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