IGFBP-3 inhibits Wnt signaling in metastatic melanoma cells.

In previous works, we have shown that insulin-like growth factor-binding protein-3 (IGFBP-3), a tissue and circulating protein able to bind to IGFs, decreases drastically in the blood serum of patients with diffuse metastatic melanoma. In agreement with the clinical data, recombinant IGFBP-3 was found to inhibit the motility and invasiveness of cultured metastatic melanoma cells and to prevent growth of grafted melanomas in mice. The present work was aimed at identifying the signal transduction pathways underlying the anti-tumoral effects of IGFBP-3. We show that the anti-tumoral effect of IGFBP-3 is due to inhibition of the Wnt pathway and depends upon the presence of CD44, a receptor protein known to modulate Wnt signaling. Once it has entered the cell, IGFBP-3 binds the Wnt signalosome interacting specifically with its component GSK-3β. As a consequence, the β-catenin destruction complex dissociates from the LRP6 Wnt receptor and GSK-3β is activated through dephosphorylation, becoming free to target cytoplasmic β-catenin which is degraded by the proteasomal pathway. Altogether, the results suggest that IGFBP-3 is a novel and effective inhibitor of Wnt signaling. As IGFBP-3 is a physiological protein which has no detectable toxic effects either on cultured cells or live mice, it might qualify as an interesting new therapeutic agent in melanoma, and potentially many other cancers with a hyperactive Wnt signaling

Enantiomeric Ratio Changes of Terpenes in Essential Oils from Hybrid Eucalyptus grandis × E. tereticornis and its Pure Species

Some Eucalyptus species produce oils with biological activities and the effect of their interspecifc hybridization on the enantiomeric composition of terpenes has not been reported. The enantiomeric excesses of monoterpenes in the essential oil of Eucalyptus grandis × E. tereticornis and its parental taxa were determined by gas chromatography-mass spectrometry (GC-MS), and to resolve coelutions problems by preparative high performance liquid chromatography (HPLC)and GC-MS with two columns in series. The essential oil composition of the hybrid presented qualitative and quantitative differences with the composition of its parental taxa. Great differences were found for the enantiomeric ratio in monoterpene alcohols among the three essential oils. Our results suggest that the enantiomeric analysis can be a reliable method for the study of how theinterspecifc hybridization can module the enantiomeric chemical profle in Eucalyptus essential oils. These results suggest the use of interspecifc hybridization to improve or expand the source of bioactive compounds.Fil: Naspi, Cecilia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Alvarez Costa, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Lucia, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Gonzalez Audino, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Masuh, Hector Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentin

Characterising the effect of semantic and perceptual similarity in episodic memory

This thesis investigated the contribution of semantic and perceptual similarity to mnemonic discrimination, defined as the ability to recognize previously encountered events and to discriminate them from similar ones to avoid false recognition. When mnemonic discriminations fails, false recognition of similar events is typically attributed to shared memory representations (gist) typically characterized in terms of meaning. In two experiments with young adults, I investigated the effects of multiple semantic and perceptual relations in a mnemonic discrimination task involving pictures of objects. I hypothesised that semantic meaning could be processed at least at two different levels: at the concept level, semantic similarity captures features shared by different concepts. I derived this continuous measure from the Conceptual Structure Account, a feature-based model of semantic memory. At the item level, rated semantic similarity between a depicted exemplar and people’s internal representation of that concept captures the degree to which an item activates its individual representation. For each item, I also measured indexes of visual form and colour similarity. In all the experiments of the current thesis, the study phase was followed by a recognition memory test including studied items, similar lures, and novel items. In Experiment 1 and 2 of Chapter 2 participants studied single and multiple exemplars for each basic-level concept, respectively. Participants were less likely to recognize studied items with high concept confusability, but also to falsely recognize these lures. Thus, greater emphasis on coarse processing of shared features relative to fine-grained processing of individual concepts weakened the basic-level semantic gist shared between studied items and lures. In contrast, false recognition was higher for those lures judged more similar to people’s internal representation of that concept, suggesting reactivation of the studied concept at test by a different exemplar. False recognition was also more frequent for more visually confusable lures. These results suggest that multiple levels of semantic and perceptual similarity contribute to mnemonic discrimination. In Chapter 3, to understand whether initial processing of semantic and perceptual information at encoding is responsible for later true and false recognition, I ran an fMRI study that combined representational similarity analysis (RSA) with the subsequent memory paradigm. To index semantic and perceptual processing that I found relevant in Chapter 2, I created two semantic models to index coarse-grained taxonomic categories and specific object features, respectively, and two perceptual models defining visual properties, like line orientation and colour attributes. Participants encoded images of objects during fMRI scanning. Both perceptual and semantic models predicted later true memory. The strength of the neural patterns corresponding to low-level visual representations in the early visual and inferotemporal cortex was stronger for items successfully recognized versus forgotten. Similarly, greater alignment of neural patterns with object-specific semantic representations in the inferotemporal cortex also predicted true recognition. However, the strength of the neural patterns reflecting nonspecific taxonomic information was stronger for items later forgotten than remembered in ventral anterior temporal lobe, left inferior frontal gyrus and, preliminary, in the left perirhinal cortex. In contrast, inefficient visual processing in posterior regions was associated with false recognition of similar lures. The results suggest that fine-grained semantic as well as visual analysis contributes to accurate later recognition, while processing visual image detail is critical for avoiding false recognition. To conclude, in Chapter 4 I investigated whether the same semantic and perceptual variables that I found to be significant predictors of young adults’ ability to recognize previously studied items, as well as misrecognize similar lures, have a greater impact on older adults’ performance on the same task. Thus, I focused on age-related differences. Contrary to our predictions, Experiment 1 did not show any age-related differences in true and false recognition, or semantic and perceptual modulations on recognition memory. However, Experiment 2 revealed an increase in true and false recognition for more confusable concepts in the older relative to young group when multiple exemplars of each basic-level concept were presented at study. I suggested this effect to be due to a reduction of processing semantic relations across concepts. This result is consistent with gist-based theories of aging that assume that semantic gist between studied items and lures can promote true and false recognition. Altogether, the studies described in the current thesis provide evidence that multiple semantic and perceptual relations can contribute to true and false recognition of objects and that these effects are in part mediated by operation that occur during the encoding phase

PERAN BPBD KOTA PEKANBARU DALAM UPAYA PENINGKATAN KESIAPSIAGAAN PENANGGULANGAN BENCANA KEBAKARAN GEDUNG PADA SATUAN PENDIDIKAN PONDOK PESANTREN AL-KAUTSAR PEKANBARU

Bencana adalah peristiwa atau rangkaian peristiwa yang mengancam dan mengganggu kehidupan dan penghidupan masyarakat yang disebabkan, baik oleh faktor alam dan/atau faktor non alam maupun faktor manusia sehingga mengakibatkan timbulnya korban jiwa manusia, kerusakan lingkungan, kerugian harta benda, dan dampak psikologis. Penyebab banyaknya korban bencana kebakaran gedung karena kurangnya pengetahuan dan kesiapsiagaan  bencana. Oleh karena itu, sosialisasi dan simulasi mitigasi bencana kebakaran gedung penting dilakukan sejak dini untuk memperkecil risiko menjadi korban melalui pendidikan bencana di sekolah. Metode yang digunakan yaitu kualitatif yang bersifat penelitian praktik dengan batasan masalah melalui pemberian materi dan pelatihan simulasi mitigasi kebakaran gedung. Kegiatan dilaksanakan di pondok pesantren AlKautsar pada tanggal 07 Desember 2023 dengan partisipan yang terlibat sebanyak 36 orang. Melalui serangkaian tahapan yang terorganisir dengan baik, mulai dari persiapan hingga penutupan, kegiatan ini berhasil menciptakan ruang dialog dan implementasi yang positif antara penyelenggara dan peserta. Hasil penelitian menunjukkan bahwa sosialisasi dan penyuluhan kepada peserta didik dan warga sekolah mampu memberikan informasi yang relevan dan bermanfaat kepada warga sekolah dalam menanggulangi bencana untuk kedepannya. Sesi diskusi dan tanya jawab dapat menambah pengetahuan, pemahaman mendalam dan keterampilan serta meningkatkan pasrtisipasi aktif bagi peserta. Dalam jangka panjang, diharapkan peningkatan pemahaman ini dapat digunakan dalam kesiapsiagaan akan bencana kebakaran yang terjadi di sekolah. Mesikpun demikian, evaluasi terus-menerus dilakukan untuk menilai seberapa siap nya warga pondok pesantren al-kautsar dalam menghadapi kejadian bencana kebakaran

LAJU KEAUSAN PAHAT HSS PADA PROSES PEMBUBUTAN DENGAN KECEPATAN TINGGI MEMPERGUNAKAN 3 JENIS CAIRAN PENDINGIN HASIL EKSTRAKSI DARI MINYAK KELAPA

Adanya gerak relatif akan mengakibatkan gesekan sehingga memicu terjadi keausan pahat. Semakin lama proses pemotongan yang dilakukan maka keausan pahat akan mencapai batas kritis keausan tepi (flank wear), sehingga fungsi pahat menjadi tidak efektif lagi. Cara umum yang dilakukan untuk mengurangi gesekan antara pahat dan benda kerja pada proses pemotongan yaitu dengan memberikan cairan pendingin (coolant). Penggunaan cairan pendingin jenis water miscible (bromus) yang berasal dari bahan kimia berdampak negatif terhadap lingkungan dan kesehatan operator. Hal ini disebabkan karena kemampuan beradaptasi dengan lingkungan yang rendah dari cairan pendingin jenis ini. Dalam penelitian ini dikaji perbandingan nilai keuasan tepi pahat dari proses bubut dengan menggunakan cairan pendingin dari beberapa hasil ekstraksi minyak kelapa dan cairan pendingin biasa (bromus). Faktor-faktor yang mempengaruhi keausan pada pahat sebagai akibat proses pemotongan yaitu kecepatan potong, gerak makan dan kedalaman makan. Metoda Taguchi signal to noise ratio digunakan untuk melihat pengaruh dari keempat variabel tersebut terhadap nilai keausan pahat yang didapatkan. Dari hasil penelitian didapatkan pendingin yang mampu memperlambar aus nya pahat yaitu RCO (refined coconut oil). Kontribusi dari beberapa level parameter terhadap nilai keausan pahat adalah putaran spindle (n) 93,22637 %, gerak makan (f) 4,644599 %, kedalaman potong (ap) 1,831 %. Penggunaan minyak kelapa sebagai cairan pendingin mampu menekan tingkat laju keausan pahat. Kata kunci : Laju keausan pahat, cairan pendingin, minyak kelapa Pembimbing : ismet hari mulyadi,Ph.

Il Capitolo della Cattedrale nella vita economica e sociale della <i>civitas</i> reatina

The thesis is based on a documentary database, wich consist of notarial deeds produced between the twelfth and mid-fourteenth-century by episcopacy of Rieti, and preserved in the Chapter’s Archive of Rieti. The candidate has analyzed the parchment material, consisting primarily of purchases, concessions, ordination in feud, gifts, reviews of possessions, and disputes. The documents are presented in the introductory chapter of the thesis, which also focused attention to the history of the Archive. Afterwards the candidate outlines the historical of the Diocese of Rieti; in the subsequent chapter is examinated the formation process of territorial possessions of the episcopate, which took place both through inter vivos gifts of property to the church of Rieti, both through bequests. The candidate then proceeds to observe what were the forms and distribution of concessions and investiture, to identify a map of property granted by the bishop and chapter, and to consider the payment, with particular attention to two books of "Instrumenta". To complete the work described above, is shown in the appendix a complete summary of the documentary sources used in the thesis, and the complete transcription of certain acts deemed to be of significant interest

A framework for comfort assessment in buildings and districts retrofit process

The retrofit design of buildings and districts cannot exclude the occupants’ perspective if comfortable and healthy conditions have to be obtained. For this reason, the NewTREND1 project developed a collaborative platform for the energy efficient buildings and districts retrofit that includes the users’ perspective. Three modules have been developed for thermal comfort, acoustic comfort and behavioural assessment. These modules are integrated into a Simulation and Design Hub that, after gathering data from on-site measurements, builds a simulation model of the district, calculates yearly results and exposes them to the design team through a dedicated District Information Model server and user interfaces. These modules perform deep investigations on the occupants’ sensation and behaviour, based on both measured and simulated datasets and provide comparisons of comfort performances, considering different retrofit scenarios and related uncertainties. In details, the thermal comfort module performs analysis according to both predictive and adaptive models, evaluates the variability around the design conditions together with sensitivity analysis that highlights which parameters are the most critical for the retrofit design. The acoustic module provides a complete tool to predict and assess the indoor acoustic comfort, taking into account the performance of building envelope and the impact of district noise. Finally, the behavioural module empowers the building energy simulation with co-simulation capabilities that reproduces the real occupants’ behaviours in relation to comfort conditions. The final goal of the framework is to support the decision-making process in selecting the optimal retrofit option that achieves the targeted energy efficiency without infringing the occupant’s expectation in terms of comfort and well-being

Measuring Occupants' Behaviour for Buildings' Dynamic Cosimulation

Measuring and identifying human behaviours are key aspects to support the simulation processes that have a significant role in buildings' (and cities') design and management. In fact, layout assessments and control strategies are deeply influenced by the prediction of building performance. However, the missing inclusion of the human component within the building-related processes leads to large discrepancies between actual and simulated outcomes. This paper presents a methodology for measuring specific human behaviours in buildings and developing human-in-the-loop design applied to retrofit and renovation interventions. The framework concerns the detailed building monitoring and the development of stochastic and data-driven behavioural models and their coupling within energy simulation software using a cosimulation approach. The methodology has been applied to a real case study to illustrate its applicability. A one-year monitoring has been carried out through a dedicated sensor network for the data recording and to identify the triggers of users' actions. Then, two stochastic behavioural models (i.e., one for predicting light switching and one for window opening) have been developed (using the measured data) and coupled within the IESVE simulation software. A simplified energy model of the case study has been created to test the behavioural approach. The outcomes highlight that the behavioural approach provides more accurate results than a standard one when compared to real profiles. The adoption of behavioural profiles leads to a reduction of the discrepancy with respect to real profiles up to 58% and 26% when simulating light switching and ventilation, respectively, in comparison to standard profiles. Using data-driven techniques to include the human component in the simulation processes would lead to better predictions both in terms of energy use and occupants' comfort sensations. These aspects can be also included in building control processes (e.g., building management systems) to enhance the environmental and system management

Perceptual and semantic representations at encoding contribute to true and false recognition of objects

When encoding new episodic memories, visual and semantic processing are proposed to make distinct contributions to accurate memory and memory distortions. Here, we used functional magnetic resonance imaging (fMRI) and preregistered representational similarity analysis (RSA) to uncover the representations that predict true and false recognition of unfamiliar objects. Two semantic models captured coarse-grained taxonomic categories and specific object features, respectively, while two perceptual models embodied low-level visual properties. Twenty-eight female and male participants encoded images of objects during fMRI scanning, and later had to discriminate studied objects from similar lures and novel objects in a recognition memory test. Both perceptual and semantic models predicted true memory. When studied objects were later identified correctly, neural patterns corresponded to low-level visual representations of these object images in the early visual cortex, lingual, and fusiform gyri. In a similar fashion, alignment of neural patterns with fine-grained semantic feature representations in the fusiform gyrus also predicted true recognition. However, emphasis on coarser taxonomic representations predicted forgetting more anteriorly in the anterior ventral temporal cortex, left inferior frontal gyrus and, in an exploratory analysis, left perirhinal cortex. In contrast, false recognition of similar lure objects was associated with weaker visual analysis posteriorly in early visual and left occipitotemporal cortex. The results implicate multiple perceptual and semantic representations in successful memory encoding and suggest that fine-grained semantic as well as visual analysis contributes to accurate later recognition, while processing visual image detail is critical for avoiding false recognition errors

Multiple dimensions of semantic and perceptual similarity contribute to mnemonic discrimination for pictures

People often misrecognize objects that are similar to those they have previously encountered. These mnemonic discrimination errors are attributed to shared memory representations (gist) typically characterized in terms of meaning. In two experiments, we investigated multiple semantic and perceptual relations that may contribute: at the concept level, a feature-based measure of concept confusability quantified each concept’s tendency to activate other similar concepts via shared features; at the item level, rated item exemplarity indexed the degree to which the specific depicted objects activated their particular concepts. We also measured visual confusability over items using a computational model of vision, and an index of color confusability. Participants studied single (Experiment 1, N = 60) or multiple (Experiment 2, N = 60) objects for each basic-level concept, followed by a recognition memory test including studied items, similar lures, and novel items. People were less likely to recognize studied items with high concept confusability, and less likely to falsely recognize their lures. This points to weaker basic-level semantic gist representations for objects with more confusable concepts because of greater emphasis on coarse processing of shared features relative to fine-grained processing of individual concepts. In contrast, people were more likely to misrecognize lures that were better exemplars of their concept, suggesting that enhanced basic-level semantic gist processing increased errors due to gist across items. False recognition was also more frequent for more visually confusable lures. The results implicate semantic similarity at multiple levels and highlight the importance of perceptual as well as semantic relations