Artemisinin is the most successful antimalarial drug against malaria caused by Plasmodium falciparum. Despite its tremendous success and popularity in malaria therapeutics, the molecular mechanism of artemisinin’s activity is still elusive. The activation of artemisinin, i.e., cleavage of the endoperoxide bond at the infected cell that generates radical intermediates and the subsequent chemical rearrangements plays a key role in the antimalarial activities. In this work, applying state-of-the-art computational techniques based on the spin-constraint density functional theory (CDFT) along with ab initio thermodynamics, we have investigated various key steps of the molecular mechanism of artemisinin. The well-accepted artemisinin activation process is the reductive heterolytic scission of the endo-peroxide bond which is followed by subsequent chemical reactions that propagate via mono-radical intermediates. Adopting CDFT methodology, here we have investigated the possible alternative ‘biradical’ intermediates and their mechanistic pathways for the subsequent chemical reactions. The change in Gibbs free energy associated with the activation of artemisinin through homolytic-scissoring (biradical) intermediate is quite competitive and favorable compared to the reductive heterolytic-scissoring (monoradical) process. This indicates the alternative possibilities for the biradical activation process. The reported experimental EPR signals for the biradicals especially for similar anti-malarial drugs like G3-factor support our observations.

This report describes a case of a 15-year-old male with cystic fibrosis caused by N1303K and Q493X cystic fibrosis transmembrane conductance regulator (CFTR) protein variants. In this case, CFTR modulators including tezacaftor/ivacaftor and subsequently elexacaftor/tezacaftor/ivacaftor were utilized and resulted in clinical stability and improvement.

The occurrence of the PTEs contamination in the environment resulting from the point or diffuse sources increases with globalization and population growth. Anyway the benefits of home gardening for the physiological and physical well-being, as well as uncertainties regarding food supply chain in the case of Covid-19, the desire to use home-grown (local) food is increasing more and more. There is no information available on the PTE pollution of urban soils used for the food production in Slovenia. Therefore, the main goal of present study is the characterization of urban gardens and agricultural areas affected by flooded sediments. The total concentrations of PTEs in soil and sediment samples were ICP-MS. The concentrations of PTEs (As, Cd, Cr, Cu, Ni, Pb and Zn) exceeded the permissible limit values defined in Slovenian Official Gazette. To define the natural or artificial origin of PTEs, the mineralogical composition of the selected soils and sediments was determined. The results obtained in present study were correlated with the national background values measured in the upper soil horizon and showed elevated concentrations. In addition to the environmental issues, the social aspect of potential impacts of PTEs on human health and safety was investigated. The results show that despite the numerous local, national and international plans and measures, greater awareness of the general public is needed to understand the hazardous effects of PTEs and the need for appropriate management of contaminated soil in the case contaminated areas.

The study was conducted in Lake Baringo and determined quantitative relationships between water level changes, water quality, and fishery production for informed lake basin management. Long-term (2008 to 2020) data on water level, water quality, and fisheries yields from Lake Baringo were analyzed using a combination of statistical methods. Linear and waveform regression analyses described patterns of lake level fluctuations over time while, Pearson’s correlation determined the concordance of lake level changes with water quality parameters, landings, and condition of fish species. PCA results grouped the study period into different years based on annual water quality variable levels. LOWESS analysis showed the decline of annual lake level amplitude over time with peak values in 1964 (8.6 m) and 2008 (9.4 m). The waveform regression significantly modeled lake level fluctuations as indexed by annual deviations from the long-term average (DLTM) and showed a 20-year oscillation between peak water levels in the lake. There were significant positive correlations of Water Level Fluctuations (WLFs) with water quality variables and water quality index (WQI) in Lake Baringo. Linear regression analyses showed a significant concordance (p < 0.05) between the annual fishery yield and the rising WLFs (r = 0.66). Overall, the results demonstrate that WLFs of Lake Baringo are a driver of fish species biomass and physico-chemical properties of the lake. We recommend the integration of fisheries yields, water quality assessment, and WLFs modeling at different temporal scales in the management of Afrotropical lake ecosystems

BACKGROUND. Myxomatous mitral valve prolapse (MVP) and mitral-annular disjunction (Barlow disease) are at-risk for ventricular arrhythmias (VA). Fibrosis involving the papillary muscles and/or the infero-basal left ventricular (LV) wall was reported at autopsy in sudden cardiac death (SCD) patients with MVP. METHODS AND RESULTS: Twenty-three patients with VA were enrolled, including five with syncope and four with a history of SCD. Electrophysiological parameters were correlated with VA patterns, ECG inferior negative T wave (nTW), and late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance. Premature ventricular complex (PVC) burden was 12061.9±12994.6 /24 hours with a papillary-muscle type (PM-PVC) in 18 patients (68%). Twelve-lead ECG showed nTW in 12 patients (43.5%). A large Uni<8.3mV area (62.4+/- 45.5 cm2) was detected in the basal infero-lateral LV region in 12 (73%) patients, and in the papillary muscles (2.2+/-2.9 cm2) in 5 (30%) of 15 patients undergoing EAM. A concomitant Bi<1.5 mV area (5.0±1.0 cm2) was identified in 2 patients. A history of SCD, and the presence of nTW, and LGE were associated with a greater Uni<8.3mV extension: (32.8+/-3.1 cm2 vs. 9.2+/-8.7 cm2), nTW (20.1+/-11.0vs.4.1+/-3.8cm2), and LGE (19.2 ± 11.7 cm2 vs. 1.0 ± 2.0 cm2, p=0.013), respectively. All patients with PM-PVC had a Uni<8.3mV area. CONCLUSIONS: Low unipolar low voltage areas can be identified with EAM in the basal infero-lateral LV region and in the papillary muscles as a potential electrophysiological substrate for VA and SCD in patients with MVP and Barlow disease phenotype

Background: β-blockers are first-line therapy in patients with long QT syndrome (LQTS). However, β-blockers had genotype dependent efficacy (LQT1>LQT2>LQT3). Sodium channel blockers have been recommended as add-on therapy for LQT3 patients. However, the effect of sodium channel blockers in all LQT patients remains unknown. Methods: We conducted a systematic electronic search of PubMed, Embase and the Cochrane Library. Fixed effects model was used to assess the effect of sodium channel blockers on QTc, cardiac events (CEs), and the proportion of QTc≥500 ms and QTc≤460 ms in LQTS patients. Results: Pooled analysis of 14 studies with 213 LQTS patients showed that sodium channel blockers significantly shortened QTc by nearly 50 ms (MD -49.43, 95%CI -57.80 to -41.05, P<0.001), reduced the incidence of CEs (OR 0.12, 95%CI 0.04 to 0.32, P<0.001) and the proportion of QTc≥500 ms (OR 0.15, 95%CI 0.09 to 0.26, P<0.001), and increased the proportion of QTc≤460 ms (OR 18.00, 95%CI 7.49 to 43.26, P<0.001). Sodium channel blockers significantly shortened QTc both in LQT3 and non-LQT3 patients, while the QTc shortening effect in LQT3 was superior to that in non-LQT3 (57.39 ms vs. 36.61 ms). Mexiletine, flecainide, and ranolazine all significantly shortened QTc, and the QTc shortening effect by mexiletine was the best (60.70 ms vs. 49.08 ms vs. 50.10 ms). Conclusions: sodium channel blockers can be useful both in LQT3 and non-LQT3 patients. Mexiletine, flecainide and ranolazine significantly shortened QTc in LQTS patients, and the QTc shortening effect by mexiletine was the best.

In this research, dynamics, and kinetics of some metal-free organic dyes based on triphenylamine having a D-π-A type structure were investigated in the gas phase and solvent (ethanol, dichloromethane, toluene, tetrahydrofuran, chloroform, and dimethylformamide) using the quantum chemistry calculations. These structures consist of triphenylamine as the donor linked to the acceptor units of cyanoacrylic acid and benzoic acid via different π-conjugated systems. The obtained results show that TC601 dye having the ethynyl anthracene phenyl -conjugated system has the preferred charge/hole transfer properties (Ginj/Greg), which in ethanol as the solvent, the lowest values of Ginj and Greg were evaluated. Molecular spectroscopic properties of the studied dyes reveal that H-P and F-P dyes have favorable molar absorption coefficients in all media. Also, the behaviors of the light-harvesting efficiency (LHE) and incident photon to current efficiency (IPCE) as the functions of the wavelength were analyzed, which show that the presence of solvent increases the values of IPCE and LHE for most studied dyes in comparison with the gas phase. Finally, based on different analyses, TC601 as the dye and ethanol as the solvent are proposed as the preferred candidates to be applied in the DSSCs.

Role of activation of the coagulation system in the pathogenesis of urticariaTaro Yasuma,1 Corina N. D’Alessandro-Gabazza,1 Tetsu Kobayashi,2 John Morser,3 Esteban C Gabazza.1*1Department of Immunology,2Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, and Mie University Hospital, Edobashi 2-174, Tsu, Mie 514-8507, Japan.3Division of Hematology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, United States*Correspondence: Esteban C Gabazza, MD, PhD, Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Postal Code 514-8507, Tsu-city, Mie, Japan. Tel.: +81 59 231 5017; fax: +81 59 231 5225.E-mail:gabazza@doc.medic.mie-u.ac.jpWord count: 590

N-heterocyclic aromatic in anion-π interaction has been playing a crucial role in a host of chemical and biological processes. In the present contribution, several different complexes composed of N-heterocyclic anthracene C14-2mH10-2mN2m (m = 1, 2, and 3) and chloride anion are investigated at the atomic level. We find that anion-π interactions are enhanced with the increasing number of N atoms. In addition, positions of nitrogen heteroatoms also have a significant effect on this interaction. Contributions of α, β and γ N atoms are in order of Nβ>Nγ>Nα. Moreover, energy decomposition analysis indicates that electrostatic interactions are the dominant stabilizing forces when chloride anion locates above aromatic ring, while the influence of other terms becomes significant when chloride anion deviates from aromatic ring. It is worth noting that dispersion forces play an important role in those anion-π interactions.

Both the Norwegian Spring Spawning herring (Clupea harengus) and the Northeast Arctic cod (Gadus morhua) are examples of how the overexploitation of marine fish populations was leading to a strong reduction even so stock collapse, with a strong decline in the associated fisheries, followed by a recovery. Cod and herring are both part of the Barents Sea ecosystem, which experienced major warming events in the early (1920-1940) and late 20th century. While the collapse or near collapse of these stocks seems to be linked to instability created by overfishing and climate, the difference of population dynamics before and after is not fully understood. In particular, it is unclear how the changes in population dynamics before and after the collapses are associated with biotic interactions. The combination of the availability of unique long-term time series for herring and cod makes it a well-suited study system to investigate the effects of collapse. We examine how species interactions may differently affect the herring and cod population dynamic before and after a collapse. Particularly we explore, using a GAM modelling approach, how herring could affect cod and reciprocally. We found that the effect on herring of cod biomass that was generally positive (i.e., covariation) became negative after the collapse (i.e., predation or competition). Likewise a change occurred for the cod, the juvenile herring biomass that had no effect before the collapse had a negative one after. Our results indicate that population collapses may lead to altered inter-specific interactions as well as altered response to abiotic environmental variations. While the stocks are at similar abundance levels before and after the collapses the system is potentially different in its functioning and may require different management action.

We calculate the energy and Shannon entropy for a hydrogen atom confined in a dielectric spherical microcavity for the fist time. In contrast to the hydrogen atom in the vacuum microcavity, some unexpected and interesting phenomena appear: First, the turning radius for the bound energy changes from positive to negative depends on the dielectric constant of the spherical microcavity sensitively. With the increase of the relative dielectric constant, the turning radius gets larger. Second, the dielectric spherical microcavity impacts the rearrangement of the excited state energy, and breaks the energy degeneracy of the excited states. At some given radius, there is energy crossover between different orbital. Third, the dielectric in the spherical microcavity affects the Shannon entropy for the confined hydrogen atom greatly. The Shannon entropy in the vacuum microcavity is the smallest and the Shannon entropy increases with the relative dielectric constant. For smaller size spherical microcavity, the Shannon entropy change is always negative, which suggests that the electron density is localized. With the increase of the radius of the microcavity, the Shannon entropy change becomes positive, and the confinement of the electron density gets delocalized. Our results show that we can control the confining effect of the spherical microcavity on the atom by changing the dielectric. This work can guide the future experimental studies for trapping and manipulating of atoms and molecules in the external environment and has some practical applications in metrology and quantum information processing.

Faced with adverse conditions, such as winter in temperate regions or hot and dry conditions in tropical regions, many insect species enter a state of diapause, a period of dormancy associated with a reduction or arrest of physical activity, development, and reproduction. Changes in common physiological pathways underlie diapause phenotypes in different insect species. However, most transcriptomic studies of diapause have not simultaneously evaluated and compared expression patterns in different tissues. Honey bees (Apis mellifera) represent a unique model system to study the mechanisms underpinning diapause. In winter, honey bees exhibit a classic diapause phenotype, with reduced metabolic activity, increased physiological nutritional resources, and altered hormonal profiles. However, winter bees actively heat their colony by vibrating their wing muscles; thus, this tissue is not quiescent. Here, we evaluated the transcriptional profiles of flight muscle tissue and fat body tissue (involved in nutrient storage, metabolism and immune function) of winter bees. We also evaluated two behavioral phenotypes of summer bees: nurses, which exhibit high nutritional stores and low flight activity, and foragers, which exhibit low nutritional stores and high flight activity. We found winter bees and nurses have similar fat body transcriptional profiles compared to foragers, whereas winter bees and foragers have similar flight muscle transcriptional profiles compared to nurses. Additionally, differentially expressed genes were enriched in diapause-related GO terms. Thus, honey bees exhibit tissue-specific transcriptional profiles associated with diapause, laying the groundwork for future studies evaluating the mechanisms, evolution, and consequences of this tissue-specific regulation.

Undergraduate field experiences (UFEs) are a prominent element of science education across many disciplines; however, empirical data regarding the outcomes are often limited. UFEs are unique in that they take place in a field setting, are often interdisciplinary, and include diverse students. UFEs range from courses, to field trips, to residential research experiences, and thereby have the potential to yield a plethora of outcomes for undergraduate participants. The UFE community has expressed a strong interest in better understanding how to assess the outcomes of UFEs. In response, we developed a strategy by which practitioners can assess their UFE using an evidence-based, systematic and iterative approach. This essay guides practitioners through the steps of: identifying intended UFE outcomes, considering contextual factors, determining an explicit assessment approach, and using the information to inform next steps. We provide a table of common learning outcomes and potential assessment tools, vignettes to illustrate using the strategy, and suggestions for practical application of the strategy. We aim to support comprehensive and aligned assessment of UFEs, leading to more inclusive and reflective design, and ultimately improved student outcomes. We urge practitioners to move towards evidence-based advocacy for continued support of UFEs.

Aim: Prostaglandin D2 (PGD2) is implicated in the pathophysiology of inflammatory diseases. GSK3439171A is a potent, reversible, and highly selective azetidine urea inhibitor of haematopoietic prostaglandin D synthase (H-PGDS, a key promoter of PGD2 production in several inflammatory cell types). Based on favourable preclinical data, we performed a first-time-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK3439171A, and the effect of food on these parameters. Methods: This was a phase 1, randomized, double-blind, placebo-controlled, dose-escalation study. Single and repeat oral doses of GSK3439171A were administered to healthy males aged 18–65 years. Levels of inflammatory markers including tetranor-prostaglandin D metabolite (tPGDM) were measured in urine samples. Results: Sixty-six participants were enrolled, with 57 receiving GSK3439171A. Single doses (5–180 mg) and repeat once-daily doses (5 and 11 mg for 14 days; 40 mg for 7 days) were administered. Seven participants (12%) had adverse events (AEs) related to study drug, mainly drug hypersensitivity (n=4 [7%]; non-serious, transient skin rash). There were no serious AEs (SAEs) or clinically significant changes in vital signs, electrocardiogram, or laboratory parameters. Dose-proportional increases in Cmax and AUC(0–inf) were observed, and the geometric mean half-life of GSK3439171A was up to 12 hours. Results were similar when GSK3439171A was taken with or without food. No consistent suppression of tPGDM levels was observed. Conclusion: GSK3439171A was well tolerated in healthy participants and there were no SAEs. Selective inhibition of H-PGDS offers therapeutic potential for muscle-related disorders (e.g. Duchenne Muscular Dystrophy) and muscular recovery following injury.

Objective: To address the effectiveness and safety of early airway utilization of budesonide and surfactant for BPD prevention in premature infants with RDS. Methods: PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, CQ VIP and China National Knowledge Infrastructure databases were searched from the inception to May 2021. Stata 16.0 software was used for statistical analysis. Results: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway tended to have a superiority on BPD incidence (RR=0.63;95%CI:0.54～0.73, P<0.001), mortality (RR=0.63;95%CI:0.43～0.94, P=0.022) and the composite outcome of BPD or mortality (RR=0.59;95%CI:0.49～0.70, P<0.001), the reuse incidence of surfactant (RR=0.54; 95%CI:0.45～0.65, P<0.001), the duration of assisted ventilation (SMD=-1.14;95%CI: -1.58 ～ -0.70, P<0.001), invasive ventilation (SMD=-1.33;95%CI: -1.76～-0.90, P<0.001), and hospital stays (SMD=-1.20;95%CI: -1.88～-0.51, P=0.001) in preterm infants with RDS. And these benefits were not associated with increased adverse outcomes. Furthermore, a decreased incidence of PDA (RR=0.80; 95%CI:0.64～0.99, P=0.041) was found in test group. Subgroup analysis based on budesonide delivery methods (inhalation or intratracheal instillation) indicated that the decrease of mortality (RR=0.62;95%CI:0.41～0.95, P=0.026), duration of assisted ventilation (SMD=-0.95;95%CI: -1.30～-0.61, P<0.001) and hospital stays (SMD=-1.38;95%CI: -2.33～-0.43, P=0.004) were mainly in budesonide intratracheal instillation subgroup. Conclusions: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway might be an effective and safe clinical practice for BPD prevention in premature infants with RDS, especially when budesonide was delivered by intratracheal instillation.

Historically, bird song complexity was thought to evolve primarily through sexual selection on males, yet in many species both sexes sing. Previous research suggests competition for mates and resources during short, synchronous breeding seasons leads to more elaborate male songs at high latitudes. In contrast, we expect male-female song dimorphism and elaboration to be more similar at lower latitudes because longer breeding seasons and year-round territoriality yield similar social selection pressures in both sexes. However, studies seldom take both selective pressures and sexes into account. We examined song elaboration and sexual dimorphism in 15 populations of nine fairy-wren species (Maluridae), a Southern Hemisphere clade with female song. We compared song elaboration and sexual song dimorphism to latitude and life history variables tied to sexual and social selection pressures and sex roles. Our results suggest that song elaboration evolved in part due to sexual competition in males: male song variability was more positively correlated with temperate breeding and greater breeding synchrony than female song. We also found strong evidence that sex-role similarity contributed to male-female song similarity: male and female songs were shorter and more similar when parental care was more equal and when male survival was high. Contrary to Northern Hemisphere latitudinal patterns, songs were less dimorphic at higher, temperate latitudes. These results suggest that selection on song can be sex-specific, with male song elaboration favored in contexts coincident with sexual selection. However, selection pressures associated with sex-role similarity also appear to constrain sex specific song evolution and song dimorphism.

Background. This article presents a comprehensive assessment of the perfusion-functional state of the LV myocardium after direct and indirect revascularization methods at various times after surgery to evaluate the complex relationship between myocardial viability and the method of revascularization. Methods. The study included 214 patients who underwent myocardial revascularization in various ways. Gated-SPECT was performed before the operation, as well as 1 month, 6 months, 1 year, and 2 or more years after the operation. Results. The groups of patients after CABG and CABG+YurLeon had differences in SRS indicators two years after surgery: 6.58±5.37 (after CABG) and 1,57±1,12 (CABG+YurLeon)(p<0.05).The most significant changes in systolic thickening (WT) occurred in segments with an accumulation of 26-40%: 1.8±1.14 (CABG), 0.51±0.35 (CABG+YurLeon), 2.6±1.19 (PCI); and in segments 41-50%: 1.23±1.10 (CABG), 0.14±0.11 (CABG+YurLeon), 2.1±0.8 (PCI) (p<0.05).In the long-term period after revascularization, the total percentage of LV myocardial segments with “functional-perfusion mismatch” stood at: 11.08±10.69% of segments (CABG), 1.26±1.2% (CABG+YurLeon), 18.44±8.70% (PCI) (p<0.05). Conclusions. Comprehensive diagnostics of patients before surgery, including gated-SPECT, allow medical professionals to more effectively choose the method of revascularization and predict the nearest and separated results. Coronary bypass surgery together with the YurLeon technique of indirect myocardial revascularization in patients with severe diffuse lesions of the coronary artery shows more effective results than other methods of surgically treating IHD.

C-radical borylation is an significant approach for the construction of carbon−boron bond. Photochemical borylation of aryl halides successfully applied this strategy. However, precise mechanisms, such as the generation of aryl radicals and the role of base additive(TMDAM) and water, remain controversy in these reactions. In this study, photochemical borylation of aryl halides has been researched by density functional theory (DFT) calculations. Indeed, the homolytic cleavage of the C−X bond under irradiation with UV-light is a key step for generation of aryl radicals. Nevertheless, the generation of aryl radicals may also undergo the process of single electron transfer and the heterolytic carbon-halogen bond cleavage sequence, and the latter is favorable during the reaction.

While the impact of biodiversity, notably functional diversity, on ecosystem productivity has been extensively studied, little is known about the effect of individual species. Here, we identified species of high importance for productivity (key species) in over 28,000 diverse grassland communities in the European Alps, and compared their effects with those of community-level measures of functional composition (weighted means, variances, skewness, and kurtosis). After accounting for the environment, the five most important key species jointly explained more deviance than all statistics of functional composition. Key species were generally tall with high specific leaf areas. By dividing the observations according to distinct habitats, the explanatory power of all non-environmental predictors increased considerably, and the relationships between functional composition and productivity varied systematically, presumably because of changing interactions and trade-offs between traits. Our results advocate for a better consideration of species’ individual effects on ecosystem functioning in complement to community-level measures.

Objective: This cross-sectional descriptive study aimed to determine the prevalence of temporomandibular disorder (TMD) and oral parafunctions in dental assistant students and examine the effects of sex and years of education. Materials and Methods: One-hundred five dental assistant students were included in the study. The Fonseca Anamnestic Index (FAI) was used to evaluate the presence of TMD in individuals, and the Oral Habit Checklist (OBC) was used to evaluate oral parafunctions. Results: Sixty-eight individuals (64.8%) had TMD at some level. It was determined that 46 of the females, who constituted the majority of the participants, had mild-TMD, which was significantly different from the males (p<0.001). According to the OBC results, oral parafunctions were associated with TMD, with low-moderate significant correlations (p <0.05). Conclusion: Early diagnosis of temporomandibular joint problems with various questionaries in the university, especially in the young population, is vital in terms of disease prognosis and will prevent future complications.

Introduction and Aim: The publication performance is an objective indicator for individuals and institutions as well as science policy and healthy implementation of the country. We aimed to reveal the quality of the publications and citations of current urologists in Turkey. Material and Methods: The publication and citation status of one thousand and two hundred urologists between the years 2016-2020 were included in the study. Socio-demographic characteristics of urologists like age, title, type of city, geographical region of the city, and type of hospital they work in and the number of publications, citations, indexed journal publication, and the first author publication status were examined. Institution of Social Insurance database was used for sociodemographic characteristics of urologist; while PubMed and Google Scholar were used for information of publications. Results: The median age of urologists was 44 (30-76) years. The median number of publications, index journal publication, the first author publication, and citations in the relevant years were 1 (0-68), 1 (0-66), 0 (0-24), and 1 (0-1025) for years specified, respectively. The publication status was significantly higher in the groups of the age range between 30 and 40 years, associate professors (OR 44.61 and 35.97, respectively) (p<0.001). Conclusion: Publications produced in the field of urology in our country are still not of sufficient quality. Urologists between the ages of 30-40 years old, associate professors, and working in tertiary care hospitals published more articles and received more citations to these publications.

Lo scopo del presente elaborato è analizzare i trend dei parametri chimico-fisici che rientrano nella classificazione di un fiume. Questi, abbinati ad altri parametri concorrono alla determinazione finale dello Stato ecologico. Per la classificazione dello stato ecologico dei corpi idrici fluviali gli elementi fisico-chimici a sostegno del biologico da utilizzare sono costituiti dai nutrienti di cui fanno parte l'azoto ammoniacale, l'azoto nitrico ed il fosforo totale oltre all'ossigeno disciolto.Rispetto a tali elementi sono stati creati dei grafici che raffigurassero l'andamento temporale e l'andamento spaziale dei vari fiumi, partendo dai primi campionamenti avvenuti all'inizio degli anni 2000.L'obiettivo è quello di analizzare i monitoraggi avvenuti degli elementi sopra citati per avere un quadro efficace e chiaro dello stato di qualità dei corpi idrici superficiali, nel suddetto caso fiumi Campani ma l'analisi può e dev'essere estesa anche all'interno reticolo idrografico italiano.

We have created a panel of twenty-nine NF1 variant cDNAs representing benign missense (MS) variants, pathogenic MS variants, many with clinically relevant phenotypes, in-frame deletions, splice variants, and nonsense (NS) variants. We have determined the functional consequences of the variants, assessing their ability to produce mature neurofibromin and restore Ras signaling activity in NF1 null (-/-) cells. cDNAs demonstrate variant-specific differences in neurofibromin protein levels, suggesting that some variants lead to protein instability or enhanced degradation. When expressed at high levels, some variant proteins are still able to repress Ras activity, indicating that the NF1 phenotype may be due to protein instability. In contrast, other variant proteins are incapable of repressing Ras activity, indicating that some do not functionally engage Ras and stimulate GTP-ase activity. We observed that stability and Ras activity can be mutually exclusive. These assays allow us to categorize variants by functional effects, may help to classify variants of unknown significance, and may have future implications for more directed therapeutics.

From the dimensionless governing equations obtained through an adequate selection of dependent and independent dimensionless variables, and the use of spatial discrimination, the dimensionless groups that govern the solution patterns of the heat transfer problem in aquifers with horizontal flow velocity are determined. As a boundary condition on the surface, the cases of constant and harmonic temperature are studied. The emergence of a characteristic length that, in its dimensionless form, depends on the deduced groups, allows the direct determination of the water flow from experimental measurements of the temperature profiles in the classical form of the inverse problem.