6 research outputs found
Hyperforin Elicits Cytostatic/Cytotoxic Activity in Human Melanoma Cell Lines, Inhibiting Pro-Survival NF-κB, STAT3, AP1 Transcription Factors and the Expression of Functional Proteins Involved in Mitochondrial and Cytosolic Metabolism
No full textHyperforin (HPF), the main component responsible for the antidepressant action of Hypericum perforatum, displays additional beneficial properties including anti-inflammatory, antimicrobic, and antitumor activities. Among its antitumor effects, HPF activity on melanoma is poorly documented. Melanoma, especially BRAF-mutated melanoma, is still a high-mortality tumor type and the currently available therapies do not provide solutions. We investigated HPF’s antimelanoma effectiveness in A375, FO1 and SK-Mel-28 human BRAF-mutated cell lines. Cell viability assays documented that all melanoma cells were affected by low HPF concentrations (EC50% 2–4 µM) in a time-dependent manner. A Br-deoxy-uridine incorporation assay attested a significant reduction of cell proliferation accompanied by decreased expression of cyclin D1 and A2, CDK4 and of the Rb protein phosphorylation, as assessed by immunoblots. In addition, the expression of P21/waf1 and the activated form of P53 were increased in A375 and SK-Mel-28 cells. Furthermore, HPF exerts cytotoxic effects. Apoptosis is induced 24 h after HPF administration, documented by an increase of cleaved-PARP1 and a decrease of both Bcl2 and Bcl-xL expression levels. Autophagy is induced, attested by an augmented LC3B expression and augmentation of the activated form of AMPK. Moreover, HPF lowers GPX4 enzyme expression, suggesting ferroptosis induction. HPF has been reported to activate the TRPC6 Ca++ channel and/or Ca++ and Zn++ release from mitochondria stores, increasing cytosolic Ca++ and Zn++ concentrations. Our data highlighted that HPF affects many cell-signaling pathways, including signaling induced by Ca++, such as FRA1, pcJun and pCREB, the expression or activity of which are increased shortly after treatment. However, the blockage of the TRPC6 Ca++ channel or the use of Ca++ and Zn++ chelators do not hinder HPF cytostatic/cytotoxic activity, suggesting that damages induced in melanoma cells may pass through other pathways. Remarkably, 24 h after HPF treatment, the expression of activated forms of the transcription factors NF-κB P65 subunit and STAT3 are significantly lowered. Several cytosolic (PGM2, LDHA and pPKM2) and mitochondrial (UQCRC1, COX4 and ATP5B) enzymes are downregulated by HPF treatment, suggesting a generalized reduction of vital functions in melanoma cells. In line with these results is the recognized ability of HPF to affect mitochondrial membrane potential by acting as a protonophore. Finally, HPF can hinder both melanoma cell migration and colony formation in soft agar. In conclusion, we provide evidence of the pleiotropic antitumor effects induced by HPF in melanoma cells
Organisation of Construction Works of an Apartment Building with Commercial Premises
No full textKäesoleva lõputöö eesmärgiks oli lahendada äripindadega korterelamu ehituse organiseerimise plaan. Hoone kompleksi moodustavad tornid, mida ühendab kaks ühist maapealset korrust ning üks maa-alune parklakorrus.
Töö käigus koostas autor ehituseelarve, kasutades projektis olevaid töömahte ja -liike. Ehitustööde kogumaksumuseks kujunes 19 305 998 eurot, millele lisandub käibemaks 20%. Kõige kallimaks tööde liigiks on ruumitarindid ja pinnakatted, mis moodustavad 28,14% kogu eelarvest. Hoone neto ruutmeetri maksumuseks on 1 410 eurot.
Eelarve koostamise käigus leiti tööajanormide järgi ehitustööde kestvused ja brigaadi suurused. Neid kasutades on koostatud kalendergraafik. Plaanil on näidatud tööde kestvused ja seosed teiste tööliikidega. Ehitustööde algus oli 01.08.2022 ning lõpp kalendergraafiku kohaselt 14.06.2024. Maksimaalselt töötab ehitusobjektil samaaegselt 87 töölist.
Lõputööga koostati ehitusplatsi üldplaan, kus on näidatud ehitusplatsi paiknemine, soojakute paiknemine, ajutised elektriliinid ning veevarustus trassid. Elektrienergia vajaduse arvutuste kohaselt paigaldatakse objektile 200 A kaitsmega peajaotuskilp. Veevajadus arvutuste kohaselt paigaldatakse objektile 32 mm läbimõõduga PE-100 veejaotustoru. Lisaks on plaanil näidatud laoplatsid, liikumisteed ning kauba mahalaadimisala. Kuna hoone kandekonstruktsioonid moodustavad raudbetoonelemendid ning paigaldus toimub ratastelt, on ehitusobjekt varustatud tornkraanaga. Tornkraanaks on valitud Comansa 2100 seeria kraana 21LC450, mille tööraadius on 60 meetrit. Ehitusplatsi üldplaanil on näidatud tornkraana paiknemine, tema tööraadiused ja ohutsoonid.
Organiseerimisplaani juurde kuulus antud töös kaks tehnoloogiakaarti. Esimesena käsitleti raudbetoonelementide montaaži ning näitena on toodud kuuenda korruse elemendid. Esmalt kirjeldati erinevaid montaažitöid, seejärel kalkuleeritakse töömahtude järgi ajakulu ning leiti töödeks vajalikud masinad ja tööriistad. Terve korruse elementide paigaldamiseks kulub neljaliikmelisel brigaadil neli tööpäeva.
Teine tehnoloogiakaart selgitas katusetöid. Esmalt kirjeldati töid, mida teostatakse ning seejärel leiti töömahtude järgi ajakulu. Ajakulule lisaks leiti töödeks vajalikud tööriistad ja masinad. Katuse töödeks kulub neljaliikmelisel brigaadil 21 tööpäeva. Tehnoloogilised kaardid, ehitusplatsi üldplaan ja kalendergraafik on toodud töö lõpus graafilises osas.The objective of this thesis was to prepare a plan for the organisation of construction works of an apartment building with commercial premises. The building to be built is located in the city block between Mustamäe, Linnu and Vesipapi streets in Kristiine, Tallinn. The building complex comprises an eight-storey tower block and a thirteen-storey tower block connected by two shared above-ground floors and one underground car park. Commercial premises are located on the first two floors, while the remaining floors are designated as residential premises.
In the economic section, the author was tasked with outlining how the cost of the building was calculated and, on that basis, the total cost of constructing the building was determined to be 19,305,998 euros, plus VAT of 20%. The most expensive type of work is the construction of room structures and coatings, which make up 28.14% of the total budget. The net cost per square metre of the building is 1,410 euros. The author then prepared a calendar schedule that specifies the works to be carried out, their inter-linkages and the labour costs associated with each type of work. The construction works commenced on 1 August 2022 and are expected to be completed on 14 June 2024, according to the calendar schedule. The maximum number of workers simultaneously working on the construction site is 87.
As part of the thesis, a master plan of the construction site was drawn up, indicating the layout of the construction site, the locations of portable cabins, temporary power lines and water mains. The traffic management plan, loading area, storage areas and danger zones all form key parts of the construction site master plan. The planning of the construction site also involved calculating the main fuse rating for construction as well as the diameter of the water distribution pipe. Given that lifting work is carried out with a Comansa 2100 series 21LC450 tower crane with a reach of 60 metres, the fuse size of the main switchboard was determined to be 200 A. After calculations, a diameter of 32 mm was chosen for the water distribution pipe.
Two technology maps were prepared as part of the thesis. The first technology map concerns the assembly of reinforced concrete elements, with the elements of the sixth floor given as an example. First, different assembly works were described, followed by a calculation of the time required based on the volume of work and a determination of the machinery and tools necessary for carrying out the work. It takes four working days for a four-member team to install the elements of an entire floor.
The second technology map described roofing works. The works to be carried out were described first and then the time required for said works was calculated based on the volume of work. In addition to calculating the time required for works, the tools and machinery necessary for carrying out the works were also determined. It takes 21 working days for a four-member team to complete the roofing works. The technology maps, master plan of the construction site and the calendar schedule are presented in the graphic section of the thesis.
In the final section of the thesis, the author describes how the contracting method was chosen and how the main occupational and fire safety and environmental protection requirements are implemented on site
Between Bouillaud and Broca: An unknown Italian debate on cerebral localization of language
No full textFrom 1825 onward, Bouillaud began gathering clinical evidence to support the hypothesis that speech is located in the cerebral frontal lobes. His aim was to provide empirical proof to Gall's theory of a specific substratum of speech in the anterior region of the brain. A well-known discussion ensued inside the French school among supporters and detractors that went far beyond Broca's first report in 1861. Unknown is that Bouillaud's investigations on localization of articulated language also gave rise to a discussion in Italy in the same period. In particular, speech localization formed a central topic in the mid-19th century in Northern Italy mainly thanks to four physicians, Michelangelo Asson, Mosè Rizzi, Gaetano Strambio and Filippo Lussana, who reported on language-impaired patients and approached these cases in the light of Bouillaud's claims. Similarly to the French debate, the Italian medical community also included attacks and advocacies of the hypothesis of a precise localization of articulated language in the frontal lobes. However, they were mainly interested in investigating the anatomo-clinical relationships rather than in supporting Gall's organology. This Italian debate appears to be the first to have developed in the mid-19th century outside that of the French community
Mise en place d’un régime diététique faiblement allergénique chez le callithricidés sujets à des diarrhées chroniques et lancement de sa version industrielle en parc zoologique
No full textThough the appearances of digestive disorders among Callitrichids living in captivity are known in numerous zoos, their origin, probably multifactorial, has little been investigated by past or current research. Since August, 2007, the author successively implemented two Callitrichids hypoallergenic diets in Asson’s zoo. At first a home-made pulp was used during twenty months, with no side effects. Then the domestic pulp was replaced by an industrial complete diet formulated for New World Monkeys replace, also intended for Callitrichids when associated with a food complement. The industrial complete diet and the Callitrichid food complement were both formulated by the author. These diet changes, implemented in Asson Callitrichid and Saimiri groups suffering from diarrhea, give positive results. Digestives disorders completely disappeared on a long-term basis, birth rate has been kept and monkeys seem physically healthy. Seeing that before August 2007, Asson’s zoo was already using a gluten-free diet, but was still confronted with digestive disorders, this new diet highlights that certain species of Callitrichids are sensitive to other allergens: if the diet in place from now on in Asson excludes the most probable, these primates are undoubtedly not sensitive to all: the next step is to examine which of these allergens is(are) the root cause(s). In the meantime, a ration stripped of the most common allergens, seems to give a solution.Bien que les manifestations de troubles digestifs chez les Callithricidés vivant en captivité soient connues dans de nombreux zoos, leur origine probablement plurifactorielle a fait l’objet de très peu d’études par le passé. Depuis Août 2007, l’auteur de cette thèse a successivement mis en place deux régimes hypoallergéniques dans la collection de Callithricidés du zoo d’Asson. Le premier, constitué d’une ration ménagère, a été suivi pendant 20 mois sans effets secondaires. Cette ration a ensuite été remplacée par un aliment industriel pour Singes du Nouveau Monde, associé à un complément alimentaire pour Callithricidés, tous deux formulés par l’auteur. Les résultats de ces changements de régime alimentaire de la collection de Callithricidés et de Saïmiris souffrant de diarrhées chroniques à Asson se sont montrés positifs. En effet, les troubles digestifs ont disparu totalement et durablement, la natalité a augmenté et les singes sont physiquement en bonne santé. Etant donné qu’avant 2007, le parc était confronté à des troubles diarrhéiques touchant ses Callithricidés malgré l’utilisation d’une alimentation sans gluten, ce nouveau régime met en évidence que certains d’entres eux sont sensibles à d’autres allergènes. Si la ration appliquée maintenant à Asson en exclue les plus probables, ces primates ne sont sans doute pas sensibles à l’ensemble de ces derniers : il faudrait à présent déterminer précisément lequel ou lesquels de ces allergènes et/ou facteurs d’intolérance serait en cause. En attendant, un régime excluant la majorité d’entre eux semble apporter une solution
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Unlocking Opportunities: How Dual Language Immersion Can Promote Equity and Integration
No full textStudy’s Purpose:This policy brief examines the potential of Dual Language Immersion (DLI) programs to advance racial, linguistic, and socioeconomic equity in public education. While DLI has grown rapidly in the U.S. and is celebrated for promoting bilingualism and integration, concerns have emerged around access and equity especially for the historically marginalized communities these programs were originally designed to serve. This study focuses on Los Angeles Unified School District (LAUSD), home to the largest number of DLI programs in the country, to assess how these programs are shaping enrollment patterns, integration, and equitable access.Research Methods:The study analyzed two decades (2001–2002 through 2021–2022) of publicly available LAUSD enrollment data from the California Department of Education. Researchers examined demographic trends across schools with and without DLI programs, disaggregated by race/ethnicity, English Learner (EL) status, and socioeconomic status. Measures of racial, linguistic, and economic diversity included entropy, exposure/isolation, and concentration indices. A critical discourse analysis of school websites and social media content was also conducted to evaluate how information about DLI programs is communicated to families.Key Findings:The study found that while DLI programs can foster diverse learning environments, they are also increasingly vulnerable to gentrification. Enrollment trends suggest that DLI programs may be disproportionately accessed by English-dominant and more affluent families, raising concerns about equity and access. Communication strategies used by schools often reinforced these disparities, privileging certain audiences over others.Conclusion:To ensure DLI programs fulfill their promise of equity and inclusion, districts must adopt intentional outreach strategies and policies that prioritize access for language-minoritized and low-income students. Without these safeguards, DLI programs risk reproducing the very inequalities they were designed to disrupt
Racial, Linguistic, and Economic Diversity Across Schools with Two-Way Dual Language Immersion Programs: Evidence from the Los Angeles Unified School District
No full textTwo-way dual-language immersion (TWDL) programs aim to combine English speakers and speakers of a partner language in the same classroom to receive content instruction in both languages. Stated goals include bilingualism and biliteracy, high academic achievement, and sociocultural competence. In school districts aiming to reduce segregation, TWDL programs also can integrate students from diverse linguistic, racial, and economic backgrounds, although mounting evidence shows that equitable integration does not always happen. Using school-level enrollments and district data on TWDL program growth from 2000 to 2021, this paper describes enrollment and segregation patterns across the Los Angeles Unified School District elementary schools with TWDL programs. We find that elementary schools with TWDL programs are enrolling increasing numbers of racially, linguistically, and economically marginalized students and are generally more diverse than schools without TWDL programs, although there appear to be limits on the potential of TWDL programs to foster diversity, especially in a segregated urban context
