DEVELOPMENT OF ION EXCHANGE MODELS FOR WATER TREATMENT AND APPLICATION TO THE INTERNATIONAL SPACE STATION WATER PROCESSOR

The International Space Station (ISS) requires a substantial amount of potable water for use by the crew. The economic and logistic limitations of transporting the vast amount of water required onboard the ISS necessitate onboard recovery and reuse of the aqueous waste streams. Various treatment technologies are employed within the ISS water processor to render the waste water potable, including filtration, ion exchange, adsorption, and catalytic wet oxidation. The ion exchange resins and adsorption media are combined in multifiltration beds for removal of ionic and organic compounds. A mathematical model (MFBMODEL™) designed to predict the performance of a multifiltration (MF) bed was developed. MFBMODEL consists of ion exchange models for describing the behavior of the different resin types in a MF bed (e.g., mixed bed, strong acid cation, strong base anion, and weak base anion exchange resins) and an adsorption model capable of predicting the performance of the adsorbents in a MF bed. Multicomponent ion exchange ii equilibrium models that incorporate the water formation reaction, electroneutrality condition, and degree of ionization of weak acids and bases for mixed bed, strong acid cation, strong base anion, and weak base anion exchange resins were developed and verified. The equilibrium models developed use a tanks-inseries approach that allows for consideration of variable influent concentrations. The adsorption modeling approach was developed in related studies and application within the MFBMODEL framework was demonstrated in the Appendix to this study. MFBMODEL consists of a graphical user interface programmed in Visual Basic and Fortran computational routines. This dissertation shows MF bed modeling results in which the model is verified for a surrogate of the ISS waste shower and handwash stream. In addition, a multicomponent ion exchange model that incorporates mass transfer effects was developed, which is capable of describing the performance of strong acid cation (SAC) and strong base anion (SBA) exchange resins, but not including reaction effects. This dissertation presents results showing the mass transfer model's capability to predict the performance of binary and multicomponent column data for SAC and SBA exchange resins. The ion exchange equilibrium and mass transfer models developed in this study are also applicable to terrestrial water treatment systems. They could be applied for removal of cations and anions from groundwater (e.g., hardness, nitrate, perchlorate) and from industrial process waters (e.g. boiler water, ultrapure water in the semiconductor industry).

Robotic Approach in the Treatment of Locally Advanced (Stage IIIA-pN2) non Small Cell Lung Cancer after Induction Therapy

Introduction: Despite there are already many studies on robotic surgery as minimally invasive approach for non-small cell lung cancer (NSCLC) patients, the use of this technique for stage III disease is still poorly described. These are the preliminary results of our prospective study on safety and effectiveness of robotic approach in patients with locally advanced NSCLC, in terms of postoperative complications and oncological outcome. Methods: Since 2016, we prospectively investigated, using standardized questionnaire and protocol, 21 consecutive patients with NSCLC stage IIIA-pN2 (diagnosed by EBUS-TBNA) who underwent lobectomy and radical lymph node dissection with robotic approach after induction treatment. Then, we performed a matched case-control study with 54 patients treated with open surgery during the same period of time, with similar age, clinical and pathological tumor stage. Results: The individual matched population was composed of 14 robot-assisted thoracic surgery and 14 patients who underwent open surgery. The median time range of resection was inferior in the open group compared to robotic lobectomy (148 vs 229 minutes; P=0.002). Lymph nodes resection and positivity were not statistically significantly different (p=0.66 and p=0.73 respectively). No difference was observed also for PFS (P=0.99) or OS (P=0.94). Conclusions: Our preliminary results demonstrated that the early outcomes and oncological results of N2-patients after robotic lobectomy were similar to open surgery. Considering the advantages of minimally invasive surgery, robotic assisted lobectomy should be a safe approach also to patients with local advanced disease.

Small molecules exploiting emerging therapeutic opportunities for breast cancer treatment

Among the different types of breast cancer (BC), the estrogen receptor positive (ER+) subtype, which requires estrogens for its growth and proliferation, is the most common, while triple negative BC, characterized by the absence of ER, progesterone receptor and human epidermal growth factor receptor 2, often leads to poor prognosis. First-line therapies for the treatment of ER+ BC act either by suppressing estrogen production, through the inhibition of aromatase (AR) enzyme, or by blocking estrogen prooncogenic activity, via the modulation/degradation of ERs. The serious side effects and the intrinsic or acquired resistance phenomena that arise with prolonged use of these drugs limit their therapeutic application, stimulating the search for new strategies to face this disease. In this context, the development of dual acting aromatase inhibitors, able to target both the orthosteric and the recently identified allosteric pockets of AR could be an opportunity to fight ER+ BC. Another promising strategy could be the development of multitarget compounds, targeting both AR and ERs. In this scenario, here we designed and synthesized two series of new xanthones or more flexible benzophenones as potential dual acting aromatase inhibitors. Moreover, inspired from tamoxifen metabolites and a literature compound endowed with activity on both AR and ER, different structurally related series of potential multitarget compounds were developed. The biological results showed that some of the new molecules were promising candidates for further development. It was recently observed that the lately discovered histamine H4 receptor is expressed in human breast tissue, displaying a key role in biological processes mediated by histamine such as cell proliferation, senescence, and apoptosis in malignant cells, representing a potential target in triple negative BC. Thus, a broad series of methyl quinazoline sulfonamides, carrying different functional groups on the sulfonamide moiety, were designed and synthesized as potential H4 receptor ligands.

Preclinical evaluation of a MYCN-specific inhibitor for the treatment of small cell lung cancer

Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, characterized by rapid growth, early metastasis and acquired drug resistance. SCLC is usually sensitive to initial treatment, however, most patients relapse within few months; thus more effective therapies are urgently needed. Key genetic alterations very frequently observed in SCLC include loss of TP53 and RB1 and mutations in the MYC family genes (MYC, MYCL or MYCN). One of them is amplified and overexpressed in a mutually exclusive manner and represents the most prominent activating oncogene alteration in this malignancy. In particular, MYCN amplification is associated with tumor progression, treatment failure and poor prognosis. Given the role of MYCN in SCLC and its restricted expression profile, MYCN represents a promising therapeutic target; although it is considered undruggable by traditional approaches. An innovative approach to target the oncogene concerns specific MYCN expression inhibition, acting directly at the level of DNA, through an antigene peptide nucleic acid (agPNA) oligonucleotide, called BGA002. This thesis focused on the study of BGA002, as a possible targeted therapeutic strategy for the treatment of MYCN-related SCLC. In this context, BGA002 proved to be a specific and highly effective inhibitor. Furthermore, MYCN silencing induced alterations in many downstream pathways and led to apoptosis, in concomitance with autophagy reactivation. Moreover, systemic administration of BGA002 was effective in vivo as well, significantly increasing survival in MNA mouse models, even in the scenario of multidrug-resistance. In addition, BGA002 treatment successfully reduced N-Myc protein expression and, more importantly, caused a massive diminishment in tumor vascularization in the multidrug-resistant model. Overall, these results proved that MYCN inhibition by BGA002 may represent a new promising precision medicine approach, to treat MYCN-related SCLC.

The RAS-Lung project: implementing blood and tissue genotyping in KRAS-Positive non-small cell lung cancer treatment

Background: The frontline management of non-oncogene addicted non-small cell lung cancer (NSCLC) involves immunotherapy (ICI) alone or combined with chemotherapy (CT-ICI). As therapeutic options expand, refining NSCLC genotyping gains paramount importance. The dynamic landscape of KRAS-positive NSCLC presents a spectrum of treatment options, including ICI, targeted therapy, and combination strategies currently under investigation. Methods: The two-year RASLUNG project, featuring both retrospective and prospective cohorts, aimed to analyze the predictive and prognostic impact of KRAS mutations on tumor tissue and circulating DNA (ctDNA). Secondary objectives included assessing the roles of co-mutations and longitudinal changes in KRAS mutant copies concerning treatment response and survival outcomes. An external validation study confirmed the prognostic or predictive significance of co-mutations. Results: In the prospective cohort (n=24), patients with liver metastases exhibited significantly elevated ctDNA levels(p=0.01), while those with >3 metastatic sites showed increased Allele Frequency (AF) (P=0.002). Median overall survival (OS) was 7.5 months, progression-free survival (PFS) was 4.0 months, and the objective response rate (ORR) was 33.3%. Higher AF correlated with an increased risk of death (HR 1.04, p = 0.03), though not progression. Notably, a reduction in plasma DNA levels was significantly associated with objective response(p=0.01). In the retrospective cohort, KRAS and STK11 mutations co-occurred in 14/21 patients (p=0.053). STK11 mutations were independently detrimental to OS (HR 1.97, p=0.025) after adjusting for various factors. KRAS tissue AF did not correlate with OS or PFS. Within the validation dataset, STK11 mutations were significantly associated with an increased risk of death in univariate (HR 2.01, p<0.001) and multivariate models (HR 1.66, p=0.001) after adjustments. Conclusion: The RAS-Lung Project, employing innovative genotyping techniques, underscores the significance of comprehensive NSCLC genotyping. Tailored next-generation sequencing (NGS) and ctDNA monitoring may offer potential benefits in navigating the evolving landscape of KRAS-positive NSCLC treatment.

Latin American Consensus: Children Born Small for Gestational Age

Background: Children born small for gestational age (SGA) experience higher rates of morbidity and mortality than those born appropriate for gestational age. In Latin America, identification and optimal management of children born SGA is a critical issue. Leading experts in pediatric endocrinology throughout Latin America established working groups in order to discuss key challenges regarding the evaluation and management of children born SGA and ultimately develop a consensus statement. Discussion: SGA is defined as a birth weight and/or birth length greater than 2 standard deviations (SD) below the population reference mean for gestational age. SGA refers to body size and implies length-weight reference data in a geographical population whose ethnicity is known and specific to this group. Ideally, each country/region within Latin America should establish its own standards and make relevant updates. SGA children should be evaluated with standardized measures by trained personnel every 3 months during year 1 and every 6 months during year 2. Those without catch-up growth within the first 6 months of life need further evaluation, as do children whose weight is <= -2 SD at age 2 years. Growth hormone treatment can begin in SGA children > 2 years with short stature (< -2.0 SD) and a growth velocity < 25th percentile for their age, and should continue until final height (a growth velocity below 2 cm/year or a bone age of > 14 years for girls and > 16 years for boys) is reached. Blood glucose, thyroid function, HbA1c, and insulin-like growth factor-1 (IGF-1) should be monitored once a year. Monitoring insulin changes from baseline and surrogates of insulin sensitivity is essential. Reduced fetal growth followed by excessive postnatal catch-up in height, and particularly in weight, should be closely monitored. In both sexes, gonadal function should be monitored especially during puberty. Summary: Children born SGA should be carefully followed by a multidisciplinary group that includes perinatologists, pediatricians, nutritionists, and pediatric endocrinologists since 10% to 15% will continue to have weight and height deficiency through development and may benefit from growth hormone treatment. Standards/guidelines should be developed on a country/region basis throughout Latin America.

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.

Simplified Mathematical Model for an Anaerobic Sequencing Batch Biofilm Reactor Treating Lipid-Rich Wastewater Subject to Rising Organic Loading Rates

This study proposes a simplified mathematical model to describe the processes occurring in an anaerobic sequencing batch biofilm reactor (ASBBR) treating lipid-rich wastewater. The reactor, subjected to rising organic loading rates, contained biomass immobilized cubic polyurethane foam matrices, and was operated at 32 degrees C +/- 2 degrees C, using 24-h batch cycles. In the adaptation period, the reactor was fed with synthetic substrate for 46 days and was operated without agitation. Whereas agitation was raised to 500 rpm, the organic loading rate (OLR) rose from 0.3 g chemical oxygen demand (COD) . L(-1) . day(-1) to 1.2 g COD . L(-1) . day(-1). The ASBBR was fed fat-rich wastewater (dairy wastewater), in an operation period lasting for 116 days, during which four operational conditions (OCs) were tested: 1.1 +/- 0.2 g COD . L(-1) . day(-1) (OC1), 4.5 +/- 0.4 g COD . L(-1) . day(-1) (OC2), 8.0 +/- 0.8 g COD . L(-1) . day(-1) (OC3), and 12.1 +/- 2.4 g COD . L(-1) . day(-1) (OC4). The bicarbonate alkalinity (BA)/COD supplementation ratio was 1:1 at OC1, 1:2 at OC2, and 1:3 at OC3 and OC4. Total COD removal efficiencies were higher than 90%, with a constant production of bicarbonate alkalinity, in all OCs tested. After the process reached stability, temporal profiles of substrate consumption were obtained. Based on these experimental data a simplified first-order model was fit, making possible the inference of kinetic parameters. A simplified mathematical model correlating soluble COD with volatile fatty acids (VFA) was also proposed, and through it the consumption rates of intermediate products as propionic and acetic acid were inferred. Results showed that the microbial consortium worked properly and high efficiencies were obtained, even with high initial substrate concentrations, which led to the accumulation of intermediate metabolites and caused low specific consumption rates.

SMALL MAMMAL PREY SELECTION BY TWO OWL SPECIES IN SOUTHEASTERN BRAZIL

A variety of factors influence prey selection by predators. Because Barn Owls (Tyto alba) and Burrowing Owls (Athene cunicularia) differ in size and foraging tactics, we expected differential predation on small mammal prey. We hypothesized that the Barn Owl, all active predator, would prey on smaller and younger individuals than the Burrowing Owl, a sit-and-wait predator. We used pellet analyses to evaluate selection of small mammals by the two owls in relation to prey), species, age, and size at the Ecological Station of Itirapina, state of Sao Paulo, in southeastern Brazil. Small mammals constituted most of the prey individuals and biomass in the diet of Barn Owls. Although Burrowing Owls consumed a wider range of taxa, small mammals represented one-third of all biomass consumed. With respect. to small mammals, Barn Owls foraged selectively relative to prey species, size, and age. Burrowing Owls foraged opportunistically relative to prey species, but selectively relative to prey size and age. Barn Owls selected smaller and younger (juvenile and subadult) individuals of the delicate vesper mouse (Calomys tener) and Burrowing Owls preyed more oil larger and older (subadult only) individuals. morphology and behavior of both prey and predators may explain this differential predation. Our data suggest that the active predator feeds oil smaller and younger prey, and the sit-and-wait predator took relatively larger and older prey.

Melatonin treatment decreases c-fos expression in a headache model induced by capsaicin

The aim of the present work was to analyze c-fos response within the trigeminal nucleus caudalis (TNC) of pinealectomized rats and animals that received intraperitoneal melatonin, after intracisternal infusion of capsaicin, used to induce intracranial trigeminovascular stimulation. Experimental groups consisted of animals that received vehicle solution (saline-ethanol-Tween 80, 8:1:1, diluted 1:50) only (VEI, n = 5); animals that received capsaicin solution (200 nM) only (CAP, n = 6); animals submitted to pinealectomy (PX, n = 5); sham-operated animals (SH, n = 5); animals submitted to pinealectomy followed by capsaicin stimulation (200 nM) after 15 days (PX + CAP, n = 7); and animals that received capsaicin solution (200 nM) and intraperitoneal melatonin (10 mg/kg) (CAP + MEL, n = 5). Control rats, receiving vehicle in the cisterna magna, showed a small number of c-fos-positive cells in the TNC (layer I/II) as well as the sham-operated and pinealectomized rats, when compared to animals stimulated by capsaicin. On the other hand, pinealectomized rats, which received capsaicin, presented the highest number of c-fos-positive cells. Animals receiving capsaicin and melatonin treatment had similar expression of the vehicle group. Our data provide experimental evidence to support the role of melatonin and pineal gland in the pathophysiology of neurovascular headaches.

Influence of Granulometry and Organic Treatment of a Brazilian Montmorillonite on the Properties of Poly(styrene-co-n-butyl acrylate)/Layered Silicate Nanocomposites Prepared by Miniemulsion Polymerization

The influence of granulometry and organic treatment of a Brazilian montmorillonite (MMT) clay on the synthesis and properties of poly(styrene-co-n-butyl acrylate)/layered silicate nanocomposites was studied. Hybrid latexes of poly(styrene-co-butyl acrylate)/MMT were synthesized via miniemulsion polymerization using either sodium or organically modified MMT. Five clay granulometries ranging from clay particles smaller than 75 mu m to colloidal size were selected. The size of the clay particles was evaluated by Specific surface area measurements (BET). Cetyl trimethyl ammonium chloride was used as an organic modifier to enhance the clay compatibility with the monomer phase before polymerization and to improve the clav distribution and dispersion within the polymeric matrix after polymerization. The sodium and organically modified natural clays as well as the composites were characterized by X-ray diffraction analysis. The latexes were characterized by dynamic light scattering. The mechanical, thermal, and rheological properties of the composites obtained were characterized by dynamical-mechanical analysis, thermogravimetry, and small amplitude oscillatory, shear tests, respectively. The results showed that smaller the size of the organically modified MMT, the higher the degree of exfoliation of nanoplatelets. Hybrid latexes in presence of Na-MMT resulted in materials with intercalated structures. (C) 2009 Wiley, Periodicals, Inc. J Appl Polym Sci 112: 1949-1958, 2009

Advanced process of microbiological control of wastewater in combined system of disinfection with UV radiation

The purpose of this study was to present a methodology with superior efficiency for inactivating pathogenic indicators commonly found in domestic sewage. The adopted method was based on synergistic effect resulting from the introduction of a UV radiation pre-disinfection stage of sewage followed by secondary treatment. A pilot unit was installed in the sewage treatment plant of the University of Sao Paulo to simulate the combined system in full-scale operational conditions. Its performance was evaluated through microbiological examinations for determining Escherichia coli, total coliforms and coliphages. The application of UV radiation at 5.1mW/cm(2) for 10 s of exposure in the first disinfection stage was enough to reduce the surviving number of E. coli around 100 times, in comparison to the conventional method. Therefore, based on experimental data, it is possible to conclude that combining treatment and pre-disinfection stage is an effective potential technique to produce effluents with lower degree of contamination by pathogenic organisms.

Treatment of linear alkylbenzene sulfonate in a horizontal anaerobic immobilized biomass reactor

Linear alkylbenzene sulfonate (LAS) is an anionic surfactant widely used to manufacture detergents and found in domestic and industrial wastewater. LAS removal was evaluated in a horizontal anaerobic immobilized biomass reactor. The system was filled with polyurethane foam and inoculated with sludge that was withdrawn from an up flow anaerobic sludge blanket reactor that is used to treat swine wastewater. The reactor was fed with easily degradable substrates and a solution of commercial LAS for 313 days. The hydraulic retention time applied was 12 h. The system was initially operated without detergent and resulted to 94% reduction of demand. The mass balance in the system indicated that the LAS removal efficiency was 45% after 180 days. From the 109th day to the 254th day, a removal efficiency of 32% was observed. The removal of LAS was approximately 40% when 1500 mg of LAS were applied in the absence of co-substrates suggesting that the LAS molecules were used selectively. Microscopic analyses of the biofilm revealed diverse microbial morphologies and denaturing gradient gel electrophoresis profiling showed variations in the total bacteria and sulfate-reducing bacteria populations. 16S rRNA sequencing and phylogenetic analyses demonstrated that members of the order Clostridiales were the major components of the bacterial community in the last step of the reactor operation. (c) 2009 Elsevier Ltd. All rights reserved.

Toxicity-directed approach of polyester manufacturing industry wastewater provides useful information for conducting treatability studies

A broader characterization of industrial wastewaters, especially in respect to hazardous compounds and their potential toxicity, is often necessary in order to determine the best practical treatment (or pretreatment) technology available to reduce the discharge of harmful pollutants to the environment or publicly owned treatment works. Using a toxicity-directed approach, this paper sets the base for a rational treatability study of polyester resin manufacturing. Relevant physical and chemical characteristics were determined. Respirometry was used for toxicity reduction evaluation after physical and chemical effluent fractionation. Of all the procedures investigated, only air stripping was significantly effective in reducing wastewater toxicity. Air stripping in pH 7 reduced toxicity in 18.2%, while in pH 11 a toxicity reduction of 62.5% was observed. Results indicated that toxicants responsible for the most significant fraction of the effluent`s instantaneous toxic effect to unadapted activated sludge were organic compounds poorly or not volatilized in acid conditions. These results led to useful directions for conducting treatability studies which will be grounded on actual effluent properties rather than empirical or based on the rare specific data on this kind of industrial wastewater. (C) 2008 Elsevier B.V. All rights reserved.

Embrittlement of electrical steel laminations by nitrogen pick-up during heat treatment

Heat treated electrical steel laminations have shown evidence of low ductility behavior, characterized by a small number of bends till fracture, on repeated bending tests. The laminations were produced using a new grade of electrical steel with much lower aluminum content than usual. The problem happens when the oxygen potential (measured by the dew point of the atmosphere) of the heat treatment atmosphere is abnormally high. Furthermore, ductility can be restored by a low-oxygen potential heat treatment. Although the heat treatment resulted in a loss of ductility, the magnetic properties were not deteriorated. The low ductility samples always show intergranular fracture, whereas the un-treated laminations fracture by cleavage. The low ductility is associated with the formation of silicon manganese nitride precipitates formed at grain boundaries, although they are not the cause of the low ductility. Ductility could be restored by a low dew point heat treatment but the inclusions remained in the grain boundaries. The low ductility and its recovery must be ascribed to the presence of nitrogen atoms segregated to the grain boundaries when the heat treatment atmosphere has a high oxygen potential. The lack of aluminum in the composition of the steel hinders the scavenging effect of this element on nitrogen atoms in solution in the steel. (C) 2009 Elsevier Ltd. All rights reserved.