Plasma-activated liquids as promising tools for non-invasive selective treatment of epithelial ovarian cancer

Plasma medicine is a branch of plasma-promising biomedical applications that uses cold atmospheric plasma (CAP) as a therapeutic agent in treating a wide range of medical conditions including cancer. Epithelial ovarian cancer (EOC) is a highly malignant and aggressive form of ovarian cancer, and most patients are diagnosed at advanced stages which significantly reduces the chances of successful treatment. Treatment resistance is also common, highlighting the need for novel therapies to be developed to treat EOC. Research in Plasma Medicine has revealed that plasma has unique properties suitable for biomedical applications and medical therapies, including responses to hormetic stimuli. However, the exact mechanisms by which CAP works at the molecular level are not yet fully understood. In this regard, the main goal of this thesis is to identify a possible adjuvant therapy for cancer, which could exert a cytotoxic effect, without damaging the surrounding healthy cells. An examination of different plasma-activated liquids (PALs) revealed their potential as effective tools for significantly inhibiting the growth of EOC. The dose-response profile between PALs and their targeted cytotoxic effects on EOC cells without affecting healthy cells was established. Additionally, it was validated that PALs exert distinct effects on different subtypes of EOC, possibly linked to the cells' metabolism. This suggests the potential for developing new, personalized anticancer strategies. Furthermore, it was observed that CAP treatment can alter the chemistry of a biomolecule present in PAL, impacting its cytotoxic activity. The effectiveness of the treatment was also preliminarily evaluated in 3D cultures, opening the door for further investigation of a possible correlation between the tumor microenvironment and PALs' resistance. These findings shed light on the intricate interplay between CAP and the liquid substrate and cell behaviour, providing valuable insights for the development of a novel and promising CAP-based cancer treatment for clinical application.

The interplay of multiplicity and effective energy for (multi) strange hadron production in pp collisions at the LHC

The enhanced production of strange hadrons in heavy-ion collisions relative to that in minimum-bias pp collisions is historically considered one of the first signatures of the formation of a deconfined quark-gluon plasma. At the LHC, the ALICE experiment observed that the ratio of strange to non-strange hadron yields increases with the charged-particle multiplicity at midrapidity, starting from pp collisions and evolving smoothly across interaction systems and energies, ultimately reaching Pb-Pb collisions. The understanding of the origin of this effect in small systems remains an open question. This thesis presents a comprehensive study of the production of $K^{0}_{S}$, $\Lambda$ ($\bar{\Lambda}$) and $\Xi^{-}$ ($\bar{\Xi}^{+}$) strange hadrons in pp collisions at $\sqrt{s}$ = 13 TeV collected in LHC Run 2 with ALICE. A novel approach is exploited, introducing, for the first time, the concept of effective energy in the study of strangeness production in hadronic collisions at the LHC. In this work, the ALICE Zero Degree Calorimeters are used to measure the energy carried by forward emitted baryons in pp collisions, which reduces the effective energy available for particle production with respect to the nominal centre-of-mass energy. The results presented in this thesis provide new insights into the interplay, for strangeness production, between the initial stages of the collision and the produced final hadronic state. Finally, the first Run 3 results on the production of $\Omega^{\pm}$ ($\bar{\Omega}^{+}$) multi-strange baryons are presented, measured in pp collisions at $\sqrt{s}$ = 13.6 TeV and 900 GeV, the highest and lowest collision energies reached so far at the LHC. This thesis also presents the development and validation of the ALICE Time-Of-Flight (TOF) data quality monitoring system for LHC Run 3. This work was fundamental to assess the performance of the TOF detector during the commissioning phase, in the Long Shutdown 2, and during the data taking period.

On The Consistency Of Monte Carlo Track Structure Dna Damage Simulations.

Monte Carlo track structures (MCTS) simulations have been recognized as useful tools for radiobiological modeling. However, the authors noticed several issues regarding the consistency of reported data. Therefore, in this work, they analyze the impact of various user defined parameters on simulated direct DNA damage yields. In addition, they draw attention to discrepancies in published literature in DNA strand break (SB) yields and selected methodologies. The MCTS code Geant4-DNA was used to compare radial dose profiles in a nanometer-scale region of interest (ROI) for photon sources of varying sizes and energies. Then, electron tracks of 0.28 keV-220 keV were superimposed on a geometric DNA model composed of 2.7 × 10(6) nucleosomes, and SBs were simulated according to four definitions based on energy deposits or energy transfers in DNA strand targets compared to a threshold energy ETH. The SB frequencies and complexities in nucleosomes as a function of incident electron energies were obtained. SBs were classified into higher order clusters such as single and double strand breaks (SSBs and DSBs) based on inter-SB distances and on the number of affected strands. Comparisons of different nonuniform dose distributions lacking charged particle equilibrium may lead to erroneous conclusions regarding the effect of energy on relative biological effectiveness. The energy transfer-based SB definitions give similar SB yields as the one based on energy deposit when ETH ≈ 10.79 eV, but deviate significantly for higher ETH values. Between 30 and 40 nucleosomes/Gy show at least one SB in the ROI. The number of nucleosomes that present a complex damage pattern of more than 2 SBs and the degree of complexity of the damage in these nucleosomes diminish as the incident electron energy increases. DNA damage classification into SSB and DSB is highly dependent on the definitions of these higher order structures and their implementations. The authors' show that, for the four studied models, different yields are expected by up to 54% for SSBs and by up to 32% for DSBs, as a function of the incident electrons energy and of the models being compared. MCTS simulations allow to compare direct DNA damage types and complexities induced by ionizing radiation. However, simulation results depend to a large degree on user-defined parameters, definitions, and algorithms such as: DNA model, dose distribution, SB definition, and the DNA damage clustering algorithm. These interdependencies should be well controlled during the simulations and explicitly reported when comparing results to experiments or calculations.

Analysis Of Cellular Adhesion On Superhydrophobic And Superhydrophilic Vertically Aligned Carbon Nanotube Scaffolds.

We analyzed GFP cells after 24h cultivated on superhydrophilic vertically aligned carbon nanotube scaffolds. We produced two different densities of VACNT scaffolds on Ti using Ni or Fe catalysts. A simple and fast oxygen plasma treatment promoted the superhydrophilicity of them. We used five different substrates, such as: as-grown VACNT produced using Ni as catalyst (Ni), as-grown VACNT produced using Fe as catalyst (Fe), VACNT-O produced using Ni as catalyst (NiO), VACNT-O produced using Fe as catalyst (FeO) and Ti (control). The 4',6-diamidino-2-phenylindole reagent nuclei stained the adherent cells cultivated on five different analyzed scaffolds. We used fluorescence microscopy for image collect, ImageJ® to count adhered cell and GraphPad Prism 5® for statistical analysis. We demonstrated in crescent order: Fe, Ni, NiO, FeO and Ti scaffolds that had an improved cellular adhesion. Oxygen treatment associated to high VACNT density (group FeO) presented significantly superior cell adhesion up to 24h. However, they do not show significant differences compared with Ti substrates (control). We demonstrated that all the analyzed substrates were nontoxic. Also, we proposed that the density and hydrophilicity influenced the cell adhesion behavior.

Influência da redução medicamentosa da pressão intra-ocular na medida da espessura da camada de fibras nervosas da retina de olhos hipertensos e glaucomatosos pela polarimetria de varredura a laser

PURPOSE: To evaluate changes in retinal nerve fiber layer thickness as measured by scanning laser polarimetry (SLP) after the use of medication to reduce intraocular pressure (IOP) in glaucomatous or ocular hypertensive patients. METHODS: The authors prospectively enrolled 37 eyes of 37 patients in whom IOP was reduced by more than 25% after the use of medication. The images were obtained before and 15 to 30 days after the introduction of medication. The SLP parameters measured before and after the use of medication were compared using paired Student's t Test. RESULTS: The mean IOP was significantly reduced from 26.57±4.23 mmHg to 16.54 ±2.92 mmHg after the use of medication (p<0.05). None of the 10 SLP analyzed parameters was significantly affected by the reduction of IOP with medication (p>0.05). CONCLUSION: The retinal nerve fiber layer thickness, as measured by SLP, is not affected by the reduction of IOP with medication in patients with glaucoma or ocular hypertension.

Evaluation of capillaries with different inner coatings for DNA analysis using dilute polymer solutions by capillary electrophoresis

In this work three capillary columns, one with uncoated inner wall and two with covalently-bound internal coatings - poly(vinyl alcohol) (PVA) and poly(dimethylacrylamide) (PDMA) - both covalently covered - were used to separate DNA fragments and compared to DNA separation using replaceable polymer solutions. The separations were performed using hydroxyethylcellulose (HEC) (90-105 kDa) in concentrations ranging from 0.00 to 2.00% m/v. The results indicated that the separation efficiency was higher in the PVA capillary than in the PDMA in all evaluated concentrations of HEC. In addition, higher resolution was also observed in PVA-coated capillary since in PDMA the shape of the peaks was not reproducible when subsequent runs were performed. Contrary to what has previously been reported in the literature, no reasonable separation was possible in bare fused silica.

Low-Level Laser Therapy in Burning Mouth Syndrome Patients: A Pilot Study

Objective: The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on the treatment of burning mouth syndrome (BMS). In addition, the laser effect was compared on the different affected oral sites. Materials and Methods: Eleven subjects with a total of 25 sites (tongue, lower lip, upper lip, and palate) affected by a burning sensation were selected. The affected areas were irradiated once a week for three consecutive weeks with an infrared laser (lambda = 790 nm). The probe was kept in contact with the tissue, and the mucosal surface was scanned during the irradiation. The exposure time was calculated based on the fluence of 6 J/cm(2), the output power of 120 mW, and the area to be treated. Burning intensity was recorded through a visual analog scale before and after the treatment and at the 6-week follow-up. The percentage of the improvement in symptoms was also obtained. Results: Burning intensity at the end of the laser therapy was statistically lower than at the beginning (p < 0.01). Patients reported an 80.4% reduction in the intensity of symptoms after laser treatment. There was no statistical difference between the end of the treatment and the 6-week follow-up, except for the tongue site. Conclusion: Under the investigated parameters, infrared LLLT proved to be a valuable alternative for BMS treatment, providing a significant and lasting reduction in symptoms.

Low-Level Laser Intensity Application in Masseter Muscle for Treatment Purposes

Objective: This study evaluated with histochemical analysis how the number of laser applications can affect the masseter muscle. Background: In dentistry today, the laser is used in patients with temporomandibular disorders (TMDs), mainly for radiating pain in the masticatory muscles, whose origins may be associated with malocclusion, although the laser effects are not well understood on the cellular level. Materials and Methods: Thirty mice (HRS/J lineage) were randomly distributed into groups according to the number of laser applications (three, six, and 10). For each group of laser applications (experimental, n = 5), it was considered the control group (n = 5), which was not irradiated. All animals inhaled halothane (2-bromo-2-chloro-1, 1, 1-trifluoroethane, minimum 99%, Sigma Aldrich, India) before each laser irradiation performed on the left masseter muscle region, on alternate days with 20 J/cm(2), 40mW, for 20 sec. The muscle samples were collected for histochemical analysis with succinate dehydrogenase (SDH) enzyme 72 h after the last application. Results: (a) A decrease in area of light fibers type (35.91% +/- 6.9%; 32.08% +/- 6.3%, and 27.88% +/- 6.3%), according to the increase of laser applications (p < 0.05); (b) significant increase (p < 0.05) in the area of intermediate fibers, with an increase of laser application (11.08% +/- 3.9%; 16.52% +/- 5.7%, and 15.96% +/- 3.9%), although the increase with 10 applications was small; (c) area increase of dark fibers in the group with three laser applications (0.16% +/- 0.3%) (p < 0.05), and in groups with six and 10 laser applications, respectively (9.68% +/- 6.0% and 9.60% +/- 4.0%). Conclusions: The SDH enzyme activity revealed that the number of laser applications increases the metabolic pattern of the muscle fibers. A minimal difference in metabolic activity between six and 10 applications of a laser suggests that further analyses should be done to confirm that six applications are enough to produce the same clinical effects, thereby contributing data to professionals from different fields in regard to the cost-benefit ratio of this therapy.

SSSPM J1102-3431 brown dwarf characterization from accurate proper motion and trigonometric parallax

Context. In 2005, Scholz and collaborators discovered, in a proper motion survey, a young brown dwarf SSSPM J1102-3431 (SSSPM J1102) of spectral type M8.5, probable member of the TW Hydrae Association and possible companion of the T Tauri star TWHya. The physical characterization of SSSPM J1102 was based on the hypothesis that it forms a binary system with TWHya. The recent discovery of a probable giant planet with a very short-period inside the TW Hya protoplanetary disk, as well as a disk around SSSPM J1102, make it especially interesting and important to measure well the physical parameters of SSSPM J1102. Aims. Trigonometric parallax and proper motion measurements of SSSPM J1102 are necessary to test for TWA membership and, thus, to determine the mass and age of this young brown dwarf and the possibility that it forms a wide binary system with TW Hya. Methods. Two years of regular observations at the ESO NTT/SUSI2 telescope have enabled us to determine the trigonometric parallax and proper motion of SSSPM J1102. Results. With our accurate distance determination of 55.2(-1.4)(+1.6) pc and proper motions of (-67.2, -14.0) +/- 0.6 mas/yr, we could confirm SSSPM J1102 as a very probable member of TWA. Assuming the TW Hydrae association age of 5-10 Myr, the evolutionary models compared to the photometry of this young brown dwarf indicate a mass of M = 25 +/- 5 M(Jup) and an effective temperature T(eff) = 2550 +/- 100 K. Conclusions. Our parallax and proper motion determination allow us to precisely describe the physical properties of this low mass object and to confirm its TWA membership. Our results indicate that SSSPMJ1102 may be a very wide separation companion of the star TW Hya.

THE GEMINI NICI PLANET-FINDING CAMPAIGN: DISCOVERY OF A CLOSE SUBSTELLAR COMPANION TO THE YOUNG DEBRIS DISK STAR PZ Tel

We report the discovery of a tight substellar companion to the young solar analog PZ Tel, a member of the beta Pic moving group observed with high-contrast adaptive optics imaging as part of the Gemini Near-Infrared Coronagraphic Imager Planet-Finding Campaign. The companion was detected at a projected separation of 16.4 +/- 1.0 AU (0.'' 33 +/- 0.'' 01) in 2009 April. Second-epoch observations in 2010 May demonstrate that the companion is physically associated and shows significant orbital motion. Monte Carlo modeling constrains the orbit of PZ Tel B to eccentricities >0.6. The near-IR colors of PZ Tel B indicate a spectral type of M7 +/- 2 and thus this object will be a new benchmark companion for studies of ultracool, low-gravity photospheres. Adopting an age of 12(-4)(+8) Myr for the system, we estimate a mass of 36 +/- 6 M(Jup) based on the Lyon/DUSTY evolutionary models. PZ Tel B is one of the few young substellar companions directly imaged at orbital separations similar to those of giant planets in our own solar system. Additionally, the primary star PZ Tel A shows a 70 mu m emission excess, evidence for a significant quantity of circumstellar dust that has not been disrupted by the orbital motion of the companion.

Proper motions of thermally emitting isolated neutron stars measured with Chandra

The remarkable astrometric capabilities of the Chandra Observatory offer the possibility to measure proper motions of X-ray sources with an unprecedented accuracy in this wavelength range. We recently completed a proper motion survey of three of the seven thermally emitting radio-quiet isolated neutron stars (INSs) discovered in the ROSAT all-sky survey. These INSs (RXJ0420.0-5022, RXJ0806.4-4123 and RXJ1308.6+2127) either lack an optical counterpart or have one so faint that ground based or space born optical observations push the current possibilities of the instrumentation to the limit. Pairs of ACIS observations were acquired 3 to 5 years apart to measure the displacement of the sources on the X-ray sky using as a reference the background of extragalactic or remote Galactic X-ray sources. We derive 2 sigma upper limits of 123 mas yr(-1) and 86 mas yr(-1) on the proper motion of RXJ0420.0-5022 and RXJ0806.4-4123, respectively. RXJ1308.6+2127 exhibits a very significant displacement (similar to 9 sigma) yielding mu = 220 +/- 25 mas yr(-1), the second fastest measured among all ROSAT-discovered INSs. The source is probably moving away rapidly from the Galactic plane at a speed which precludes any significant accretion of matter from the interstellar medium. Its transverse velocity of similar to 740 (d/700 pc) km s(-1) might be the largest of all ROSAT INSs and its corresponding spatial velocity lies among the fastest recorded for neutron stars. RXJ1308.6+2127 is thus a middle-aged (age similar to 1 My) high velocity cooling neutron star. We investigate its possible origin in nearby OB associations or from a field OB star. In most cases, the flight time from birth place appears significantly shorter than the characteristic age derived from spin down rate. Overall, the distribution in transverse velocity of the ROSAT INSs is not statistically different from that of normal radio pulsars.

Kinetic ion effect on geodesic acoustic Alfven modes in tokamaks

Using a quasitoroidal set of coordinates with coaxial circular magnetic surfaces, the Vlasov equation is solved for collisionless plasmas, and the dielectric tensor is found for large aspect ratio tokamaks in a low frequency band. Taking into account q-profile and charge separation parallel electric field, it is found that the Alfven wave continuum is deformed by ion geodesic effects producing continuum minimum at the rational magnetic surfaces. Low frequency geodesic ion induced Alfven waves are found below the continuum minimum where collisionless damping has a gap for Maxwell distribution. In kinetic approach, the ion thermal motion defines the geodesic effect but the mode frequency is strongly corrected due to parallel motion of electrons.

Escape patterns of chaotic magnetic field lines in a tokamak with reversed magnetic shear and an ergodic limiter

The existence of a reversed magnetic shear in tokamaks improves the plasma confinement through the formation of internal transport barriers that reduce radial particle and heat transport. However, the transport poloidal profile is much influenced by the presence of chaotic magnetic field lines at the plasma edge caused by external perturbations. Contrary to many expectations, it has been observed that such a chaotic region does not uniformize heat and particle deposition on the inner tokamak wall. The deposition is characterized instead by structured patterns called magnetic footprints, here investigated for a nonmonotonic analytical plasma equilibrium perturbed by an ergodic limiter. The magnetic footprints appear due to the underlying mathematical skeleton of chaotic magnetic field lines determined by the manifold tangles. For the investigated edge safety factor ranges, these effects on the wall are associated with the field line stickiness and escape channels due to internal island chains near the flux surfaces. Comparisons between magnetic footprints and escape basins from different equilibrium and ergodic limiter characteristic parameters show that highly concentrated magnetic footprints can be avoided by properly choosing these parameters. (c) 2008 American Institute of Physics.

Neutrino and antineutrino inclusive charged-current cross section measurements with the MINOS near detector

The energy dependence of the neutrino-iron and antineutrino-iron inclusive charged-current cross sections and their ratio have been measured using a high-statistics sample with the MINOS near detector exposed to the NuMI beam from the main injector at Fermilab. Neutrino and antineutrino fluxes were determined using a low hadronic energy subsample of charged-current events. We report measurements of nu-Fe ((nu) over bar - Fe) cross section in the energy range 3-50 GeV (5-50 GeV) with precision of 2%-8% (3%-9%) and their ratio which is measured with precision 2%-8%. The data set spans the region from low energy, where accurate measurements are sparse, up to the high-energy scaling region where the cross section is well understood.

Charged hadron multiplicity fluctuations in Au+Au and Cu+Cu collisions from root S(NN) = 22.5 to 200 GeV

A comprehensive survey of event-by-event fluctuations of charged hadron multiplicity in relativistic heavy ions is presented. The survey covers Au+Au collisions at s(NN)=62.4 and 200 GeV, and Cu+Cu collisions at s(NN)=22.5,62.4, and 200 GeV. Fluctuations are measured as a function of collision centrality, transverse momentum range, and charge sign. After correcting for nondynamical fluctuations due to fluctuations in the collision geometry within a centrality bin, the remaining dynamical fluctuations expressed as the variance normalized by the mean tend to decrease with increasing centrality. The dynamical fluctuations are consistent with or below the expectation from a superposition of participant nucleon-nucleon collisions based upon p+p data, indicating that this dataset does not exhibit evidence of critical behavior in terms of the compressibility of the system. A comparison of the data with a model where hadrons are independently emitted from a number of hadron clusters suggests that the mean number of hadrons per cluster is small in heavy ion collisions.