Dose Planning Evaluation of Intensity-Modulated Proton Therapy (IMPT) Technique Based on In-House Dynamic Thorax Phantom

One of the drawbacks of the Intensity Modulated Radiation Therapy (IMRT) technique is that the absorbed dose in healthy tissue is relatively high. Proton beam has characteristics that can compensate for these drawbacks. The Bragg peak characteristic of a proton beam allows the administration of high radiation doses to the target organ only. Non-Small Cell Lung Cancer (NSCLC) cases are located in the vicinity of many vital organs, so radiation doses that exceed a certain limit will have a significant impact on these organs. Proton is a heavy particle that exhibits interaction patterns with tissue heterogeneity that differ from that of photon. This study aims to determine the distribution of proton beam planning doses in the NSCLC cases with the Intensity Modulated Proton Therapy (IMPT) technique and compare its effectiveness with the IMRT technique. Treatment planning was done by using TPS Eclipse on the water phantom and on the in-house thorax dynamic phantom. The water phantom planning parameters used are one field at 0° and three fields at 45°, 135°, and 225°. In this study, a single, sum, and multiple field techniques on the in-house thorax dynamic phantom were used. The evaluation was performed by calculating Conformity Index (CI), Homogeneity Index (HI), and Gradient Index (GI) parameters for each treatment planning. As a result, a bit of difference in the CI the HI values are shown between IMPT and IMRT planning. The GI values of IMPT planning are in the range between 4.15-4.53, while the GI value of IMRT is 7.89. The histogram results of the planar dose distribution show that the IMPT treatment planning provides fewer off-target organ doses than the IMRT planning. Evaluation was also carried out on the    IMPT treatment planning of target organs in five areas of interest and four OAR positions. The evaluation results were then compared with the IMRT measurement data. As a result, the value of the point doses at the target organ      did not differ significantly. However, the absorbed dose with the IMPT technique at four OAR positions is nearly zero, which had a large difference compared to the IMRT technique

Unifying gauge couplings at the string scale

Using the current precision electroweak data, we look for the minimal particle content which is necessary to add to the standard model in order to have a complete unification of gauge couplings and gravity at the weakly coupled heterotic string scale. We find that the addition of a vector-like fermion at an intermediate scale and a non-standard hypercharge normalization are in general sufficient to achieve this goal at two-loop level. Requiring the extra matter scale to be below the TeV scale, it is found that the addition of three vector-like fermion doublets with a mass around 700 GeV yields a perfect string-scale unification, provided that the affine levels are $(k_Y, k_2 ,k_3)=(13/3, 1, 2)$, as in the $SU(5) \times SU(5)$ string-GUT. Furthermore, if supersymmetry is broken at the unification scale, the Higgs mass is predicted in the range 125 GeV - 170 GeV, depending on the precise values of the top quark mass and $\tan \beta$ parameter.Comment: 11 pages, 4 eps figures, using jpconf style, talk given at CORFU2005, RTN meeting ``The Quest for Unification: Theory Confronts Experiment'', 11 - 18 September 2005, Corfu, Greec

Impact of Smoking Habit on Peri-Implant Indicators following Different Therapies: A Systematic Review

Peri-implant disease and its treatment is becoming a major concern for clinicians as the number of implants placed each year is rising. Smoking is a common habit, and it is associated with an increased risk of developing peri-implant disease. The role of smoking in the response to peri-implant treatment has never been investigated. Searches were conducted in electronic databases to screen articles published until August 2021. The included studies had at least two groups of patients: peri-implant disease only or peri-implant disease and smoking status. Outcomes of interest included plaque index (PI), probing depth (PD), bleeding on probing (BoP), radiographic crestal bone loss (CBL), and analysis of peri-implant sulcular fluid. Seven hundred and forty-nine articles were found in the databases, only 71 articles potentially qualified. A total of seven studies with a minimum follow-up of six months were included. There is no homogeneity in the diagnosis, smoker definition and treatment proposed. All surgical and non-surgical treatment have statistically significantly different outcomes in smokers and nonsmokers. Recognizing this study's limitations, we conclude that smoking might play a significant role on the outcome of peri-implant disease treatment. None of the proposed treatments appear to be significantly more effective

Top quark physics in hadron collisions

The top quark is the heaviest elementary particle observed to date. Its large mass makes the top quark an ideal laboratory to test predictions of perturbation theory concerning heavy quark production at hadron colliders. The top quark is also a powerful probe for new phenomena beyond the Standard Model of particle physics. In addition, the top quark mass is a crucial parameter for scrutinizing the Standard Model in electroweak precision tests and for predicting the mass of the yet unobserved Higgs boson. Ten years after the discovery of the top quark at the Fermilab Tevatron top quark physics has entered an era where detailed measurements of top quark properties are undertaken. In this review article an introduction to the phenomenology of top quark production in hadron collisions is given, the lessons learned in Tevatron Run I are summarized, and first Run II results are discussed. A brief outlook to the possibilities of top quark research a the Large Hadron Collider, currently under construction at CERN, is included.Comment: 84 pages, 32 figures, accepted for publication by Reports on Progress in Physic

Characteristics of air/water slug flow in an intermediate diameter pipe

Experiments have been carried out in a 67 mm diameter pipe with air and deionised water in which gas superficial velocities between 0.04 and 0.55 m/s were studied. A capacitance technique, employing electrodes mounted on either side of the outside of the acrylic resin pipe, has been used to provide time varying cross-sectionally averaged void fraction. Probability Density Functions of these data has permitted characterisation of the slug flow. Pressure drop measurements were made using differential pressure transducer. The mean void fraction, the void fraction in the slug region, the slug velocity and the dimensionless length of liquid slug all increase with the superficial gas velocity. On the other hand increasing the superficial gas velocity was shown to decrease the fractional slug length, the frequency and the film thickness around the Taylor bubble as well as the pressure gradient. A new version of the drift flux equation for bubble rise velocity is proposed and found to perform well against the present data and that from the literature

March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity.

In transplantation, donor dendritic cells (do-DCs) initiate the alloimmune response either by direct interaction with host T cells or by transferring intact donor MHC to host DCs. However, how do-DCs can be targeted for improving allograft survival is still unclear. Here we show CD103+ DCs are the major do-DC subset involved in the acute rejection of murine skin transplants. In the absence of CD103+ do-DCs, less donor MHC-II is carried to host lymph nodes, fewer allogenic T cells are primed and allograft survival is prolonged. Incubation of skin grafts with the anti-inflammatory mycobacterial protein DnaK reduces donor MHC-II on CD103+DCs and prolongs graft survival. This effect is mediated through IL-10-induced March1, which ubiquitinates and decreases MHC-II levels. Importantly, in vitro pre-treatment of human DCs with DnaK reduces their ability to prime alloreactive T cells. Our findings demonstrate a novel therapeutic approach to dampen alloimmunity by targeting donor MHC-II on CD103+DCs

Autophagy induced by Helicobacter pylori infection is necessary for gastric cancer stem cell emergence

Background: The main cause of gastric cancer is the infection by the bacterium Helicobacter pylori which induces a chronic inflammation and an epithelial-to-mesenchymal transition (EMT) leading to the emergence of cells with cancer stem cell (CSC) properties. However, the underlying mechanisms have not been fully characterized. Moreover, H. pylori modulates the host cell autophagic process, but a few studies have investigated the role of this process in tumoral transformation. The aim of this study was to determine whether H. pylori-induced autophagy has a role in CSC emergence. Methods: Autophagic flux in response to H. pylori infection was characterized in AGS cell line expressing the tandem-tagged mCherry-GFP-LC3 protein and using a ratiometric flow cytometry analysis. Then, AGS and MKN45 cell lines were treated with bafilomycin or chloroquine, two pharmaceutical well-known inhibitors of autophagy, and different EMT and CSC characteristics were analyzed. Results: First, a co-expression of the gastric CSC marker CD44 and the autophagic marker LC3 in mice and human stomach tissues infected with H. pylori was observed. Then, we demonstrated in vitro that H. pylori was able to activate the autophagy process with a reduced autophagic flux. Finally, infected cells were treated with autophagy inhibitors, which reduced (i) appearance of mesenchymal phenotypes and migration ability related to EMT and (ii) CD44 expression as well as tumorsphere formation capacities reflecting CSC properties. Conclusion: In conclusion, all these data show that H. pylori-induced autophagy is implicated in gastric CSC emergence and could represent an interesting therapeutic target.This work was supported by the French foundation Ligue contre le Cancer (Pyrénées Atlantiques)

Immunophenotyping and Efficacy of Low Dose ATG in Non-Sensitized Kidney Recipients Undergoing Early Steroid Withdrawal: A Randomized Pilot Study

Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings. Trial Registration ClinicalTrials.gov NCT0054840

Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine

Background: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. Methods: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. Findings: After eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001). Interpretation: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. Funding: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy

Axion Models with High-Scale Supersymmetry Breaking

Inspired by the possibility of high-scale supersymmetry breaking in the string landscape where the cosmological constant problem and the gauge hierarchy problem can be solved while the strong CP problem is still a challenge for naturalness, we propose a supersymmetric KSVZ axion model with an approximate universal intermediate-scale ($\sim 10^{11}$ GeV) supersymmetry breaking. To protect the global Peccei--Quinn (PQ) symmetry against quantum gravitational violation, we consider the gauged discrete $Z_N$ PQ symmetry. In our model the axion can be a cold dark matter candidate, and the intermediate supersymmetry breaking scale is directly related to the PQ symmetry breaking scale. Gauge coupling unification can be achieved at about $2.7\times 10^{16}$ GeV. The Higgs mass range is 130 GeV to 160 GeV. We briefly discuss other axion models with high-scale supersymmetry breaking where the stabilization of the axion solution is similar.Comment: RevTex4, 24 pages, 3 figures, typos corrected, references adde