Auswahl der wissenschaftlichen Literatur zum Thema „FISIC platform“

The design and performances of a newly built electrostatic charge state analyzer constructed to act as a spectrometer for keV/u ions are reported. It consists of two 90∘ curved electrodes enclosed by Matsuda electrodes. This setup was recently tested using Ar9+ and Ar12+ ion beams at an energy of 10 keV per charge unit. This spectrometer achieves a good separation of different charge states formed by electron capture processes during collisions between primary ions and the residual gas. Thanks to these first tests, we have identified up to three different background contributions on the detector that need to be reduced or suppressed.

Pola berbelanja terus berevolusi karena perilaku konsumen yang semakin rumit, di mana konsumen tidak hanya melakukan pembelian sebagai kebiasaan tetapi juga berdasarkan pada kondisi dan situasi tertentu. Pembelian impulsif adalah salah satu dari peristiwa yang banyak mempengaruhi individu. Meskipun pembelian impulsif dapat memberikan keuntungan bagi produsen dan pemasar, hal ini dapat menimbulkan masalah bagi konsumen karena seringkali dilakukan tanpa perencanaan dan dapat mengakibatkan dampak negatif. Penelitian ini bertujuan untuk menganalisis pengaruh faktor situasional terhadap perilaku pembelian impulsif di platform belanja online Shopee, dengan fokus pada generasi Milenial berusia 25 sampai 40 tahun di Tangerang. Faktor situasional yang diteliti meliputi lingkungan fisik, lingkungan sosial, perspektif waktu, dan suasana hati.. Dengan tujuan untuk mengungkapkan bagaimana faktor-faktor tersebut mempengaruhi keputusan pembelian impulsif. Menggunakan metode kuantitatif dengan pendekatan non-probabilitas teknik purposive sampling, yaitu sampel akan dipilih berdasarkan pertimbangan khusus. Dianalisis menggunakan SmartPLS versi 3.0, penelitian ini menganalisis data dari 150 responden yang memenuhi kriteria tertentu, termasuk usia, kepemilikan akun di Shopee, dan pernah bertransaksi pada platform Shopee. Hasil menunjukan bahwa pembelian impulsif dipengaruhi oleh lingkungan fisik, lingkungan sosial, perspektif waktu dan suasana hati. Responden menunjukan kecenderungan untuk membeli produk yang tidak mudah rusak dan seringkali secara impulsif saat merasa bosan atau bahagia. Analisis ini menunjukan bahwa lingkungan fisik dan perspektif waktu memiliki pengaruh yang signifikan pada pembelian impulsif, sementara lingkungan sosial tidak memiliki pengaruh signifikan. Penelitian ini memberikan pemahaman yang mendalam tentang faktor-faktor yang mendorong perilaku pembelian impulsif di platform Shopee.

Emas merupakan logam mulia yang banyak diminati, karena umumnya harga cenderung stabil dan meningkat setiap tahun. Investasi emas terbagi menjadi dua, ada investasi digital dan investasi fisik. Seringkali dalam investasi digital investor mengalami kerugian. Hal ini di karenakan banyak investor yang tidak mampu untuk memprediksi trend harga emas baik secara personal maupun menggunakan tools yang sudah ada. Studi ini bertujuan untuk memprediksi harga emas menggunakan Algoritma Genetika dan Algoritma Multiple Linear Regression (MLR). Hasil akhir penelitian ini membuktikan algoritma genetika memiliki akurasi terbaik..

The development of technology and the internet has changed the consumer paradigm in making purchases, especially through online platforms such as Lazada. This research aims to examine the influence of online customer reviews and ratings on purchasing decisions on the Lazada marketplace, with a focus on students at the Faculty of Social and Political Sciences, University of Riau who use the Lazada application. The research method used was a survey via questionnaire distributed to 300 student respondents. Data analysis was carried out using multiple linear regression techniques to test the research hypothesis. The research results show that online customer reviews and online customer ratings have a significant influence on purchasing decisions at Lazada. This shows that online customer reviews and ratings play an important role in shaping buyers' perceptions of the products offered on the platform.

Rumah sakit diharapkan memberikan kemudahan akses kepada seluruh lapisan masyarakat. Penyandang disabilitas merupakan bagian dari masyarakat yang memiliki keterbatasan, baik secara fisik, sensorik, dan/atau intelektual. Keterbatasan tersebut menyebabkan penyandang memerlukan alat bantu yang menyebabkan hambatan arsitektural. khususnya dalam mengakses ruangan secara vertikal. Dibutuhkan alat bantu atau pengganti transportasi vertikal yang bertujuan memudahkan para penyandang disabilitas, khususnya tunadaksa, dalam mengakses ruangan secara vertikal. Transportasi vertikal seperti tangga akan sulit digunakan oleh pengguna kursi roda secara mandiri. Solusi untuk permasalahan tersebut adalah dengan menambahkan d lift tangga, platform lift dan/atau memberikan fasilitas ramp. Dengan mempertimbangkan unsur aksesibilitas, ramp berperan penting dalam membantu penyandang disabilitas terlebih pada perancangan rumah sakit karena tidak ada waktu tunggu dan ruang lebih dalam tanah. Ramp selain dapat digunakan sebagai akses vertikal, jika di desain dengan baik akan dapat digunakan sebagai sarana penyembuhan pasien. Kekurangan dari ramp adalah pengguna memerlukan tenaga lebih dibandingkan dengan platform lift dan lift tangga, penambahan kedua akses vertikal tersebut pada ramp akan sangat membantu mempermudah penyandang disabilitas. Penelitian ini dilakukan untuk mempelajari alat bantu dan pengganti transportasi vertikal yang aman digunakan oleh penyandang disabilitas dan dapat diterapkan pada perancangan rumah sakit. Hasil temuan dari penelitian ini akan digunakan sebagai referensi untuk perancangan tugas akhir peneliti. Metode penelitian yang digunakan adalah metode penelitian studi pustaka. Data akan dikumpulkan dan dianalisis secara menyeluruh lalu disintesis untuk mendapatkan temuan baru. Penelitian dilakukan saat terjadinya pandemi COVID-19 yang menyebabkan keterbatasan ruang gerak juga terdapat batasan waktu untuk menyelesaikan penelitian.

Abstract. SMEs maklun screen printing t-shirt services are MSMEs that provide services for the production of screen printing t-shirts. The emergence of changes in current business conditions on the part of MSMEs and problems with the ordering information service system complicate the running of the business and can even make the business not get a good system value, of course there must be improvements to lead to an effective and efficient system. the problem is formulated "What kind of Information System Design is needed with the use of a free platform on the service of ordering information and services at SMEs on screen printing shirts". Researchers use the prototype method because the testing phase is very suitable for the design model of this method. This method has four main stages, the first stage of planning (planning) identification with system requests and feasibility studies. The second stage is analysis (analysis) to analyze business processes and identify system requirements as well as logical modeling of system and user interactions, as well as data modeling. The third (design) doing physical data modeling and physical process models. The fourth stage is (implementation) building a system using multiple platforms. The results of the study explain the concept of business processes in the process, interaction and data are easier to access, systematic exchange of information, connected data storage facilitates data management, reduces direct information exchange activities or information exchange without any data records, consumer trial phase using database Free platforms have also been met, namely caspio, weebly, Zapier, Spreadsheet, Canva, tawk.to and Google data studio dashboards. Abstrak. UMKM jasa maklun kaos sablon merupakan umkm penyedia layanan jasa pembuatan produksi kaos sablon. Munculnya perubahan keadaan bisnis saat ini di pihak umkm dan permasalahan pada sistem pelayanan informasi pemesanan mempersulit berjalannya bisnis bahkan dapat membuat binis tidak mendapatkan nilai sitem yang baik tentunya harus ada perbaikan untuk mengarah ke sistem yang efektif dan efisien. Berdasarkan fenomena tersebut, maka permasalahan yang dirumuskan “Perancangan Sitem Informasi seperti apa yang dibutuhkan dengan pemanfaatan platform gratis pada pelayanan pemesanan jasa maklun di UMKM kaos sablon”. Peneliti menggunakan metode prototype karena tahap pengujian sangat cocok digunakan untuk model perancangan metode ini. Metode ini memiliki empat tahapan utama yaitu Tahap pertama perencanaan (planning) melakukan identifikasi dengan system request dan studi kelayakan. Tahap kedua yaitu analisis (analysis) melakukan analisis terhadap proses bisnis dan identifikasi kebutuhan sistem serta pemodelan logis interaksi sistem dan penggunanya, serta pemodelan data. Tahap ketiga yaitu perancangan (design) melakukan pemodelan data fisik dan model proses fisik. Tahap keempat yaitu (implementation) membangun sistem menggunakan multi platform. Hasil penelitian menjelaskan konsep proses bisnis dalam proses, interaksi dan data lebih dipermudah dalam pengaksesan, pertukan informasi yang sistematis, penyimpanan data yang terhubung mempermudah pengelolaan data, mengurangi aktivitas pertukaran informasi secara langsung atau pertukaran informasi tanpa ada record data, tahap uji coba konsumen menggunakan basis platform gratis juga telah terpenuhi yaitu caspio, weebly, Zapier, Spreadsheet, Canva, tawk.to dan Google data studio sebagai dashboard infografis.

Dari hasil studi dan penelitian tentang pendidikan pria atau wanita di lingkungan keluarga, sekolah dan masyarakat, penting bagi pria atau wanita siswa yang baik secara mental maupun fisik. Sekolah individu dengan literasi virtual adalah upaya untuk memenuhi penggunaan literasi virtual di dunia serba teknologi saat ini dan merupakan proyek untuk instruktur. Lingkungan keluarga dan fakultas sendiri harus diselaraskan untuk menjadi jembatan pada tahap selanjutnya dalam membentuk orang siswa yang diinginkan sehingga digitalliteracy dapat terlaksana di SMA 3 Palangka Raya. Karena minat mereka untuk lebih memahami, keluarga dan perguruan tinggi mendorong siswanya untuk melakukan digitalliteracy SMA 3 Palangka Raya.

This study aims to identify the effect of using a digital economic platform on the performance of SMEs in Palembang City. The existence of the Covid 19 Pandemic that has taken place since the beginning of 2020 has encouraged the acceleration of the digital economy in the form of a digitalization process in a wider scope such as work, consumption, social relations, and the use of time by the community. Consumption patterns that were previously carried out by the public physically, are now switching online and digitally. SMEs that are targeted in this research are culinary SMEs in the city of Palembang. The selection of culinary SMEs was carried out because of the rapid growth of culinary SMEs in the city of Palembang. This study will identify the influence of SMEs that utilize digital platforms on performance during the pandemic. The digital economy platform is measured through the digital platform capability variable, while the performance of SMEs is through the sales of SMEs during the pandemic. Then in looking at these variables, there is the ability of the network as a mediating variable and the age of SMEs and the size of SMEs as control variables. The results showed that platform capability had a significant effect on the performance variable of SMEs with a 95% confidence level. Likewise with network capabilities as a mediating variable between Platform capabilities and performance. Thus, it can be said that during the Covid-19 pandemic, Platform Capability will improve the performance of SMEs by increasing the network capabilities or network capabilities of these SMEs. Kata Kunci : Economics Platform, Digital Platform, Platform Capability, Network Capability, SMEs Performance Abstrak Penelitian ini bertujuan untuk mengidentifikasi pengaruh pemanfaatan platform ekonomi secara digital terhadap kinerja UMKM di Kota Palembang. Adanya Pandemi Covid 19 yang berlangsung sejak awal tahun 2020 mendorong akselerasi ekonomi digital berupa proses digitalisasi dalam ruang lingkup yang lebih luas seperti pekerjaan, konsumsi, hubungan social ataupun pemanfaatan waktu senggang oleh masyarakat. Pola konsumsi yang sebelumnya dilakukan oleh masyarakat secara fisik, kini beralih secara online dan digital. UMKM yang menjadi sasaran dalam penelitian ini adalah UMKM kuliner yang berada di Kota Palembang. Pemilihan UMKM kuliner dilakukan dikarenakan pesatnya pertumbuhan UMKM kuliner yang ada di Kota Palembang. Dalam penelitian ini akan diidentifikasi pengaruh UMKM yang memanfaatkan platform digital terhadap kinerja usahanya selama pandemic berlangsung. Platform ekonomi digital diukur melalui variable kemampuan platform digital sedangkan kinerja UMKM diukur melalui hasil penjualan UMKM selama pandemic. Kemudian dalam melihat hubungan variable-variabel tersebut terdappat kemampuan jaringan sebagai variable mediasi serta usia UMKM dan ukuran UMKM sebagai variable control. Hasil penelitian menunjukkan bahwa Platform capability berpengaruh secara signifikan terhadap variable kinerja UMKM dengan tingkat kepercayaan 95%. Begitu dengan network capability sebagai variable mediasi antara Platform capability dan kinerja. Dengan demikian dapat disimpulkan bahwa selama pandemic Covid-19 Platform Capability akan meningkatkan kinerja UMKM dengan meningkatkan kapabilitas kemampuan jaringan atau network capability dari UMKM tersebut. Kata Kunci : Platform Ekonomi, Platform Digital, Platform Capability, Network Capability, Kinerja UMKM

Sekolah dasar yang berpartisipasi dalam gerakan literasi Kabupaten Probolinggo sangat penting untuk mensukseskan program kemitraan. SD Namira Kecamatan Kraksaan Kabupaten Probolinggo merupakan rekanan bisnis awal. Program “Gadget Positive Literacy Culture School” saat ini sedang dilaksanakan di SDN Namira Kecamatan Kraksaan Kabupaten Probolinggo dalam rangka menumbuhkan kecintaan membaca dan menulis di kalangan siswa SD. Karena berbagai alasan, sekolah telah memutuskan untuk memberikan instruksi dalam program Pembelajaran Berbasis Kecerdasan Buatan yang tersedia di platform Sekolah Literasi Digital melalui adaptasi dari platform e-learning pemerintah Indonesia, Rumah Belajar. Dengan sedikit keberuntungan, pelatihan ini akan membekali para pendidik untuk tetap mengajar meski harus berpisah secara fisik akibat pandemi Covid-19. Gubernur Jawa Timur telah mengeluarkan surat edaran yang meminta orang tua untuk mengeluarkan anak-anak mereka dari sekolah untuk sementara waktu. Oleh karena itu, salah satu prinsip dasar dari filosofi kami sebagai sebuah organisasi adalah bahwa cara terbaik bagi sekolah dan orang tua untuk mendukung perkembangan akademik anak-anak mereka adalah dengan bekerja sama untuk memungkinkan anak-anak menerima pendidikan. pendidikan dalam kenyamanan rumah mereka sendiri. Hal ini dapat dicapai melalui penggunaan metode pendidikan yang lebih konvensional, seperti menghadiri kelas di lokasi fisik, atau, baru-baru ini,. Salah satu aspek yang membantu lembaga mitra ini adalah adanya elemen infrastruktur E-Learning. E-Learning adalah metode pengajaran yang menggabungkan instruksi kelas tradisional dengan pengaturan diskusi dan kolaborasi online yang lebih informal. Pernyataan E-Government pemerintah Indonesia secara maksimal, program yang berbasis pada platform Sekolah Literasi Digital berbasis Artificial Intelligence ini dapat melatih dan mulai menjadikan siswa di sekolah menjadi individu yang memiliki kepribadian berpikir kritis dan responsif. Platform pembelajaran yang dikenal sebagai "Rumah Belajar." Selanjutnya, sekolah akan menawarkan program pelatihan untuk platform pembelajarannya, yang akan didasarkan pada kecerdasan buatan, sehingga memecahkan masalah. Platform Indonesia akan dioptimalkan untuk mencapai tujuan ini. Pendidikan Online Pemerintah "Rumah Belajar".

Outfit Of The Day (OOTD) fashion information is part of students' daily lives. Searching for online fashion information is often done before making a decision when shopping online. This research aimed to determine the fashion information-seeking behavior of FISIP students, Universitas Bengkulu in following OOTD trends. Research method was quantitative with a survey method through population was 2,731 students from 6 departments and sample of 96 respondents. Research results showed that FISIP students often look for information on fashion and shopping on the Internet. The e-commerce platform Shopee and social media Instagram were the media most often used to find information. Students' information-seeking behavior was categorized as quite good, with a score of 3,16. Women and men only had a slight difference: women more often searched for fashion information on the Internet.The FISIP students often use the Internet to look for information on fashion. Online shopping was the main choice compared to shopping in physical stores directly. The platform most often used to search for fashion information e-commerce was Shopee. Students would buy clothes, shoes and accessories. Students chose online shopping accounts that were most visited and used by buyers online. Before deciding to buy, students paid attention to reviews and ratings from online stores in e-commerce. In conclusion the information-seeking behavior of FISIP students at Universitas Bengkulu is in a good category, as they have gone through stages of information-seeking behavior when looking for information on fashion trends before deciding to buy.

Étudier les collisions ion-atome et ion-ion permet d'appréhender les probabilités des processus électroniques tels que la capture, l'ionisation et/ou l'excitation en maîtrisant le nombre d'électrons initialement liés à chaque partenaire de la collision. En allant de l'étude d'un système à trois corps (les deux noyaux avec un seul électron) vers des systèmes plus complexes impliquant des électrons supplémentaires permet d'examiner des effets sur la dynamique globale des électrons et par conséquent sur les sections efficaces des processus élémentaires.Dans la section théorique de la thèse, des calculs de sections efficaces sont effectués pour des systèmes ion-atome et ion-ion contenant jusqu'à deux électrons. Le carbone, l'hydrogène, l'azote et l'hélium ont été choisis comme partenaires de collision. Cela est réalisé en utilisant une approximation semi-classique non perturbative, qui consiste à traiter le mouvement des ions de manière classique, tandis que la dynamique des électrons est décrite en utilisant la mécanique quantique. Les collisions sont simulées à l'aide d'un programme “collision solver”, à partir duquel des sections efficaces pour différents processus peuvent être extraites.La partie expérimentale de la thèse est dédiée au développement technique, aux tests et à la caractérisation de divers instruments essentiels pour la réalisation d'expériences précises de collision ion-atome et ion-ion. Deux sources d'ions et les lignes de faisceau correspondantes ont été installées pour réaliser des collisions ion-ion garantissant qu'une large gamme de conditions expérimentales et de types de collisions. Une chambre de collision, un jet gazeux, un spectromètre d'ions et son détecteur associé, un système de détection de rayons X ont été développés et caractérisées pour réaliser les premières études.Dans l'ensemble, cette thèse combine de nouveaux calculs théoriques pour les collisions ion-atome et ion-ion avec des avancées expérimentales vers une configuration capable d'explorer une large gamme de systèmes de collision. Cette double approche est très bénéfique pour améliorer la compréhension de la dynamique des électrons dans les collisions ion-matière. Ces connaissances sont essentielles tant pour la recherche fondamentale que pour les applications pratiques dans divers domaines scientifiques et technologiques, tels que les plasmas astrophysiques, la recherche sur la fusion par confinement inertiel ou encore l'hadronthérapie
Studying ion-atom and ion-ion collisions allows us to understand the probabilities of electronic processes such as capture, ionization, and/or excitation by controlling the number of electrons initially bound to each collision partner. By progressing from the study of a three-body system (the two nuclei with a single electron) to more complex systems involving additional electrons, we can examine the effects on the overall electron dynamics and consequently on the cross-sections of elementary processes.In the theoretical section of the thesis, cross-section calculations are performed for ion-atom and ion-ion systems containing up to two electrons. Carbon, hydrogen, nitrogen, helium and their respective ions have been chosen as collision partners. This is achieved using a semi-classical non-perturbative approach: the relative motion of the partners is treated classically, while the electron dynamics is described quantally. The collisions are simulated using a “collision solver” program, from which cross sections for different processes can be extracted.The experimental part of the thesis is dedicated to the technical development, rigorous testing, and thorough characterization of various instruments critical for conducting precise ion-atom and ion-ion collision experiments. Two ion sources and their respective beamlines were set up to perform ion ion collisions, ensuring a large range of possible experimental conditions and collision systems can be explored. A collision chamber, gaseous jet, an ion spectrometer and its associated detector, as well as an x-ray detection system were developed and characterized to perform the preliminary experiments.Overall, this thesis combines new theoretical calculations for ion-atom and ion-ion collisions with experimental advancements towards a set-up capable of exploring a wide range of collision systems. The dual approach is very beneficial for enhancing the understanding of electron dynamics in ion-matter collisions. This knowledge is essential for both fundamental research and practical applications in various scientific and technological fields, such as astrophysical plasma, inertial confinement fusion research or hadrontherapy

The use of nanocarriers for drug delivery and imaging purposes have highly increased in the last decades. Both hard and soft matter-based formulations can provide selective and efficient treatment in several administration routes. Indeed, the biocompatibility and the biodegradability of the formulations represent a key requirement in order to translate the in vitro studies into in vivo investigations. Therefore, lipids are a safe choice as building blocks to formulate a large variety of liquid crystalline architectures in water. Vesicles, hexosomes and cubosomes have been adopted as nanomedicine platforms providing excellent biological performances. However, several drawbacks may impact the application of these carriers: the poor stability in the physiological environment and the biodegradability of the stabilizing agent required to sterically stabilized the nanoparticles (NPs) are few examples. Given the importance these materials have acquired nowadays in the nanomedicine field, this thesis is devoted to investigating on the factors that can enhance the physico-chemical and biological performances of these nanoparticles for systemic and topical administration. Most of the formulations presented in this thesis were prepared using monoolein as building block, given its biocompatibility and lower cytotoxicity in comparison with other surfactants. However, the potential application of cell-derived nanoparticles known as nanoerythrosomes for medical imaging was also explored. Therefore, the thesis evaluated different approaches: (i) evaluation of the effect of various stabilizers (modified poloxamers, hemicellulose and polyphosphoesters) on monoolein-based cubosomes features, in order to formulate nanoparticles suitable for systemic administration. This investigation was focused on the physico-chemical (bulk and surface) characterization of the empty carriers and of those loaded with antioxidants or fluorophores suitable for in vitro imaging. Bioassays (viability and uptake experiments) were conducted in order to evaluate the biological performance of the differently stabilized cubosomes. (ii) the effect of permeation enhancers and edge activators on monoolein-based vesicles and hexosomes for topical administration. In vitro permeation tests were performed to show the efficacy of these carriers into overcoming the stratum corneum, the first layer of the skin, to deliver antioxidants. (iii) the potential role of nanoparticles derived from red blood cells, nanoerythrosomes, as personal medicine for application in optical imaging. Cross-linking and Click Chemistry were employed to decorate the surface of the nanoparticles and their emission properties in a physiological buffer were evaluate.

Il presente lavoro di tesi nasce come collaborazione tra il Laboratorio di Progettazione Elettronica e il Laboratorio di Microscopia a Fluorescenza del Dipartimento di Fisica e Astronomia dell' Università di Bologna. In particolare nasce dalla volontà di dotare il dipartimento di un apparato sperimentale in grado di svolgere studi sulla Galvanotassia, un fenomeno biologico consistente nella migrazione di cellule sottoposte a stimolazione elettrica. La Galvanotassia è nota da fine '800 ma non sono ancora chiari i meccanismi cellulari che la provocano. Una migliore comprensione di tale fenomeno potrebbe portare importanti sviluppi in ambito medico, sia diagnostici che terapeutici. Dalla letteratura a riguardo non è emersa l'esistenza di apparecchi elettronici di controllo che permettano lo studio della Galvanotassia e che possano essere duttili a seconda del tipo di esperimento che si voglia svolgere. Da qui l'idea di iniziare lo sviluppo di un dispositivo elettronico, che fosse riprogrammabile, a basso costo e facilmente trasportabile. La progettazione di questo dispositivo ha portato ad una prima fase di test e verifiche sperimentali che hanno permesso di migliorare e affinare la costruzione di uno strumento di misura e controllo dei parametri relativi alla Galvanotassia. Sono già stati programmati test futuri che porteranno ad una versione definitiva dell' apparecchiatura alla quale succederanno più approfondite ricerche sul fenomeno della Galvanotassia.

A multilayered dielectric structure, namely a one dimensional photonic crystal (1DPC), is proposed as a suitable platform for photon management, due to the low absorption of the dielectric materials. When properly designed, a 1DPC can sustain surface electromagnetic modes called Bloch Surface Waves (BSWs). In this PhD Thesis it is shown how light coupled to BSW can be focused or guided by means of ultrathin polymeric refractive structures directly patterned on the surface. Moreover, by patterning the surface with surface relief gratings, far-field radiation can be efficiently coupled to the surface modes, thus providing an enhanced electromagnetic field at the truncation interface of the 1DPC. By shaping the grating in a circular symmetry, light can be in-plane focused into a sub-wavelength spot. The same structure can be used to re-shape the radiation pattern of dipolar emitters. It is shown that an emitter lying on the surface of the 1DPC couples to the photonic structure and the fluorescence radiated couple with the surface modes. The so called BSW-coupled fluorescence propagates along the surface with low losses and a well-defined wavevector. By means of surface diffraction gratings properly designed, fluorescence can be extracted along any direction, thus improving the fluorescence collection with no need of high numerical aperture optics or critical alignements. A novel method for evaluating the enhancement gained with such photonic structures on the extraction efficiency is proposed. Such method is capable of providing at the same time spatial resolution, angular resolution and spectral resolution. A biosensing experiment to detect small amounts of labeled proteins is provided, in order to show the sensing capabilities of the photonic structure.

Early detection of cancer plays a crucial role in determining disease prognosis. The major challenge consists in the ability of identifying the disease through the quantification of a set of specific biomarkers in tissues and/or, more interestingly, released in the bloodstream. Non-invasiveness, sensitivity, parallelization, low cost, are some of the most relevant keywords in this field. Hence the development of miniaturized devices for the early detection of cancer is at the core of nanodiagnostics, requiring the recognition and quantification of low amounts of specific disease biomarkers, through the development of sensitive diagnostic tools. In this context, we have developed a nanodiagnostic platform for the non-invasive quantification of cancer biomarkers circulating in the bloodstream. The assay, that relies on Atomic Force Microscopy (AFM), is based on molecular manipulation to create density-optimized functional spots of surface-immobilized binders and differential AFM topography. It is label-free, allows the parallel detection of different cancer biomarkers, entails a single binder per antigen and when implemented with fluorescence labelling/readout can be used for epitope mapping. The possibility to exploit DNA nanografting and subsequent immobilization of binders through DNA-directed immobilization confers robustness to the assay. We explored the feasibility of novel binders as camelid nanobodies and aptamers, to improve the quality of the functionalization, and therefore device sensitivity, with the added advantage of binders easy engineering. In this study we focused on a prospective, clinically-relevant circulating cancer biomarker, the extra-cellular domain (ECD) of Human Epidermal Growth Factor Receptor (Her2), whose shedding and release in the blood is related to the progression of Her2-positive tumors and response to anticancer therapies. By employing robust, easily engineered camelid nanobodies as binders, we measured ECD-Her2 concentrations in the range of the actual clinical cutoff value for Her2 positive breast cancer. The specificity for Her2 detection was preserved when measured in complex matrices as standardized human serum, and in parallel with other potential biomarkers, demonstrating the intended implementation of multiplexing analysis, strongly required to define the biological tumor subtype and to univocally refer specific molecular levels to tumor status and progression. A better understanding of the Her2 receptor biology, overexpression in tumor cell membranes and release of the ECD to the bloodstream is however required to interpret the measured levels of ECD-Her2 at best. At present, there are controversial studies and conflicting results about the correlation between the protein levels in serum and the attested Her2 status in tumor tissue, which make the clinical significance of circulating ECD-Her2 still uncertain. Therefore we developed a multi-integrated approach in order to elucidate Her2 overexpression, dimerization and ECD shedding mechanism and to fully validate its prognostic value; moreover we preliminarily studied some fundamental aspects of the relationship between rafts-mediated exosomes formation and Her2 integration on them in order to clarify its possible role in metastasis occurrence. This approach relies on different multi-scale techniques and enables to correlate information coming from advanced optical microscopies (membrane proteins localization), nanotechnology-based diagnostic tools (detection of protein and vesicle biomarkers) and novel super resolution fluorescence microscopies (quantification and co-localization of different biomarkers). This innovative platform will be instrumental in identifying and quantifying clinically useful biomarkers and to translate basic science results into the clinics to impact cancer diagnosis, prognosis, and therapy.

In questa tesi magistrale ho studiato e analizzato gli strumenti e le risorse offerte dalla piattaforma di e-learning MOODLE e verificato quali opportunità offre per l'insegnamento e l'apprendimento. Ho effettuato, tenendo conto di queste risorse e di concetti di didattica della fisica, il trasferimento di uno dei corsi presenti sul sito ISHTAR dell'Università di Bologna, facendone la traduzione in inglese e integrandolo con elementi multimediali e forme di interfaccia, verifica e comunicazione proprie della piattaforma. Per un secondo corso, ho studiato e confrontato diverse metodologie di implementazione, basate su diversi obiettivi educativi.

2012/2013
Le proteine intrinsecamente disordinate (IDP), nello stato nativo non ripiegate, sono inclini all’aggregazione e direttamente correlate con lo sviluppo di malattie amiloidi. Tra queste, ci siamo focalizzati sullo studio dell’alfa-Sinucleina (AS), una proteina coinvolta nella malattia di Parkinson, un disturbo neurodegenerativo caratterizzato dalla degenerazione dei neuroni dopaminergici e l’accumulo di AS in placche amiloidi. Sebbene lo studio delle interazioni AS-dopamina sia di importanza cruciale nella comprensione dei meccanismi responsabili dello sviluppo della malattia, tuttavia, non sono disponibili dati in letteratura riguardo all’affinità di questo legame nei diversi stati ripiegati/funzionali dell’AS. L’elevata tendenza all’aggregazione delle IDP rende difficile il loro studio in soluzione e anche una stima approssimativa dei parametri relativi all’affinità di legame è estremamente difficile. Nuove tecniche di superficie potrebbero pertanto permettere lo studio delle interazioni di legame di molecole e di farmaci capaci di favorire/inibire l’aggregazione. In particolare, le tecniche di superficie potrebbero permettere un migliore controllo dell’immobilizzazione di queste proteine, particolarmente instabili in soluzione, e di studiare con alta precisione fenomeni di legame. Con questa visione, la microscopia di forza atomica (AFM) rappresenta un’opportunità. Il nanografting, una tecnica litografica per mezzo AFM, permette l’immobilizzazione di proteine orientate con il preciso controllo dei parametri di immobilizzazione. Con AFM e AFM-nanografting, abbiamo prodotto una nuova piattaforma per lo studio di diversi aspetti dell’aggregazione/interazione dell’AS. Abbiamo quindi studiato l’affinità di legame tra AS e dopamina misurando variazioni nell’altezza e nella rugosità della topografia AFM su AS immobilizzata in aree confinate, in funzione della concentrazione di dopamina. Il valore micromolare della costante di dissociazione (Kd) è stato inoltre confermato dallo studio dello spiazzamento di un anticorpo legato all’AS in seguito all’aggiunta di dopamina. Sebbene la Kd calcolata con il nostro approccio sia una stima della reale Kd calcolata in soluzione, in quanto influenzata dall’affollamento delle molecole o ai limiti di diffusione, i nostri risultati sono comunque degni di nota. Infine, abbiamo testato il nostro saggio per lo studio delle fasi preliminari dell’aggregazione dell’AS. In particolare, abbiamo osservato come aggregati confinati di AS siano disciolti dall’azione della dopamina, confermando il suo ruolo nell’inibizione della fibrillazione. In questo modo, abbiamo creato un saggio potenzialmente utilizzabile per lo screening di nuove molecole che interagiscono con l’AS ed eventualmente utilizzabili come farmaci. Inoltre, l’interazione di AS con microdomini della membrana cellulare (lipid rafts) sono oggetto di dibattito. Per questo motivo, abbiamo utilizzato dei doppi strati lipidici modello con composizione capace di mimare quella dei lipid rafts. In particolare, abbiamo caratterizzato con AFM e GISAXS (Grazing Incidence Small Angle X-ray Scattering) delle membrane lipidiche di tre componenti, aventi separazione di fase lipidica, studiando l’effetto dell’umidità e della percentuale di colesterolo su ciascuna fase. Abbiamo quindi studiato l’effetto del legame dell’AS su questo sistema modello. In particolare, immagini di topografia AFM in liquido ci hanno dato la possibilità di discriminare la topografia di strutture filamentose formatesi inseguito all’interazione di AS. Il fenomeno, dipendente dalla fase lipidica della membrana e quindi dall’ordine delle molecole, sembra essere favorito da un blando impacchettamento dei lipidi. Inoltre, utilizzando misure GISAXS, è stato possibile determinare un considerevole riordinamento della membrana in seguito al legame di AS.
Intrinsically disordered proteins (IDPs) are natively unfolded, prone to aggregation and directly correlated with amyloid diseases. Among them, we focused on alpha-Synuclein (AS), a protein related to Parkinson’s disease, a neurogenerative disorder characterized by the degeneration of dopaminergic neurons and the accumulation of AS into amyloid plaques. In particular, the study of AS-dopamine (DA) adducts is crucial for the comprehension of the mechanisms responsible of Parkinson’s disease development. However, according to our knowledge, there is no evidence in literature about AS-DA binding parameters at different folding/functional state of AS. IDPs have in fact a strong propensity to aggregate, making it extremely difficult to get even rough estimation of binding affinities in solution. Therefore, new methods able to study surface immobilized IDPs could be useful for both fundamental studies of binding interactions and drug screening of new compounds able to interact favouring/inhibiting the aggregation process. In particular, the use of a surface-based technique could help to better control the immobilization of such proteins, particularly unstable in solution, and to study with high precision binding events. With this perspective, atomic force microscopy (AFM) offers a challenge. Nanografting, an AFM mediated nanolithographic technique, allows for the nanoscale immobilization of proteins in a well-oriented manner with the precise control of the immobilization parameters. By means of AFM and AFM-nanografting, we produced a new platform able to study different aspects of AS aggregation/interactions. First, we studied AS-dopamine binding affinity by measuring the variation of AFM topographic height on AS nanopatches due to binding of DA on the patch as a function of its concentration in solution, and the correspondent surface roughness variation. The value of the dissociation constant, in the micromolar range, was confirmed by studying the displacement of AS-bound mAbs, after the addition of dopamine. We think that this result is noteworthy, even though we are aware that the Kd values obtained with our assay are probably a very rough estimate of the Kd of the AS/DA interaction occurring in solution, due for instance to AS surface crowding and restrictions to diffusion. Finally, the assay was used to study the early stages of the aggregation process. In particular, dopamine dissolved confined AS aggregates confirming its role in the inhibition of fibrillation. In this way, we created a potential screening assay able to study the interaction of AS with new molecules virtually usable as new drugs. Moreover, the interaction of AS with lipid rafts, specialized microdomains of the cell membrane, is object of a strong debate. For this reason, we created a model supported lipid bilayer with composition able to mimic lipid rafts. In particular, we characterized by both AFM and Grazing Incidence Small Angle X-ray Scattering (GISAXS) a three components membrane presenting a lipid phase separation, focusing on the effect of humidity and cholesterol percentage on the structure of each phase. Then, we studied the effect of AS binding on this membrane model system. In particular, trough AFM imaging in liquid we discriminated the topology of filamentous structures resulting from AS binding. The phenomenon is dependent on the membrane’s lipid phase and order and is favoured by mild packing of lipids. From GISAXS measurements, the occurrence of a strong rearrangement of the membrane upon AS binding was suggested.
XXVI Ciclo
1984

Optofluidics is a promising interdisciplinary research and technological field, thanks to its wide potential of application in sector like medicine, chemistry, biology and environmental science. In this context the study of innovative materials including their properties, their efficiency, their limits and their possibility of leading to miniaturized devices is the key point for the overcoming of currently adopted strategies. A promising material that could satisfy new optofluidic requirements is Lithium Niobate (LiNbO3 - LN) thanks to its excellent optical and nonlinear optical properties. In this work we demonstrated for the first time the applicability of the Lithium Niobate as a high intagrable and tailorable substrate for optofluidics. As a matter of fact, we developed all the several stages that can be interconnected to realize a platform with complex optofluidic functionalities: from the droplets generation and manipulation, to their transfer through a microfluidic channel directly engraved on the crystal substrate, to the droplets optical analysis stage. In particular in this thesis we present the first high performant T-Junction droplet generator completely engraved in LN, and the first Ti in-diffused channel waveguide coupled with a microfluidic channel in the same substrate. Furthermore a study on the wetting properties of the Lithium Niobate is discussed. Concerning the optical stage we discuss the realization of optical frequency converter realized in LN, which plays a key role in the development of our optofluidic platform. In fact it can be used to integrate a laser source in the green-blue range that could found application particularly in the biological field. Moreover we present the first frequency converter in the PPLN configuration realized in Zirconium doped LN, a dopants that prevent the optical damage and therefore could increase the intensity of work and the efficiency of conversion of the devices. Also we implemented the process to produce single-mode channel waveguide by Ti in-diffusion as interconnection stage for the optical circuit. Concluding, we were able to implement a well-equipped tool-box for the incorporation of different devices on the same substrate, demonstrating for the first time the integration of all the different stages in a single substrate, and paving the way to an extreme optofluidic integration in Lithium Niobate.
L’optofluidica è un promettente settore di ricerca interdisciplinare con altrettante interessanti applicazioni tecnologiche. Questo grazie al suo ampio potenziale in settori quali la medicina, la chimica, la biologia e le scienze ambientali. In questo contesto uno studio di materiali innovativi che includa le loro proprietà, la loro efficienza, i loro limiti e la loro possibilità di produrre dispositivi miniaturizzati è fondamentale per superare le attuali strategie adottate. Un materiale promettente per soddisfare i requisiti dell’optofluidica è il Niobato di Litio (LN o LiNbO3), un materiale conosciuto per le sue eccellenti proprietà ottiche lineari e non lineari e che qui discutiamo per la prima volta in un contesto optofluidico. In questo lavoro abbiamo dimostrato l’applicabilità del Niobato di Litio come substrato altamente integrabile e adattabile per l’optofluidica. Abbiamo infatti sviluppato tutti i diversi stadi che possono essere interconnessi per realizzare una piattaforma con funzionalità complesse optofluidiche: dalla produzione di gocce, alla loro manipolazione, al loro trasporto in canali microfluidici realizzati nel cristallo, fino all’analisi ottica delle stesse. In particolare nella tesi sono presentati il primo generatore di gocce a giunzione a T completamente fabbricato su Niobato di Litio e la prima guida d’onda a canale in Titanio diffuso accoppiata con un canale. Infine abbiamo proposto il primo studio completo sulla bagnabilità del Niobato di Litio. Per quanto riguarda lo stadio ottico, abbiamo realizzato dei convertitori di frequenza ottica, dispositivi che giocano un importante ruolo nel progetto, in quanto possono essere usati come sorgenti laser integrate con emissione nell’intervallo verde-blu, uno spettro che trova molte applicazioni nell’ambito biologico. In questo contesto abbiamo realizzato il primo convertitore di frequenza con configurazione PPLN realizzato su Niobato di Litio drogato Zirconio, un nuovo tipo di drogante che prevenendo il danno ottico è in grado di aumentare l’intensità di lavoro e l’efficienza di conversione di questi dispositivi. Abbiamo infine implementato il processo per produrre guide ottiche a canale monomodo per diffusione di Titanio, dispositivi necessari per connettere le diverse parti del circuito ottico. In conclusione con questo lavoro abbiamo implementato un’ampia categoria di dispositivi, per la prima volta tutti contemporaneamente integrabili su un singolo substrato. Abbiamo perciò aperto la strada verso un’elevata integrazione di funzionalità optofluidiche su Niobato di Litio.

Parkinson’s disease (PD) current clinical management is mostly based on patient’s subjective report about the effects of treatments and on medical examinations that unfortunately represent only a snapshot of a highly fluctuating clinical condition. This traditional approach requires time, it is biased by patient’s judgment and is often not completely reliable, especially in moderate advanced stages. The main purpose of the EU funded project PD_manager (Horizon 2020, Grant Agreement n° 643706) is to build and evaluate an innovative, mHealth, patient-centric system for PD remote monitoring. After a first phase of research and development, a set of wearable devices has been selected and tested on 20 patients. The raw data recorded have been used to feed algorithms necessary to recognize motor symptoms. In parallel, other applications have been developed to test also the main non-motor symptoms. On a second phase, a case- control randomized multicentric study has been designed and performed to assess the acceptability and utility of the PD_manager system at patients’ home, compared to the current gold standard for home monitoring, represented by symptoms diaries. 136 couples of patients and caregivers have been recruited, and at the end of the trial the system was found to be very well tolerated and easy to use, compared to diaries. The developed System is able to recognize motor and non-motor symptoms, helping healthcare professionals in taking decisions on therapeutic strategies. Moreover, PD_manager could represent a useful tool for patient's self-monitoring and self-care promotion.