Parte A: Divide et impera: tramite uno screening in silico che targhetta l'omodimerizzazione del fattore di processività di HCMV, ppUL44, sono state identificate piccole molecole inibenti la replicazione virale. ParteB: Identificazione del proteoma nucleare di tutti i virus umani tramite un'analisi completa della localizzazione nucleare classica.

Human cytomegalovirus (HCMV) è un agente patogeno principale di molte malattie in persone immunosoppresse, inclusi pazienti affetti da AIDS e sottoposti a trapianto, e nascituri congenitamente infetti. Le terapie ed i farmaci antivirali utilizzati per il trattamento dell’infezioni da HCMV presentano una serie di limitazioni, tra cui la bassa biodisponibilità, tossicità, e l’insorgenza di ceppi virali farmaco resistenti, rendendo cruciale la necessità di identificare nuovi target terapeutici efficaci. Studi sulle interazioni tra proteine virali (PPI) si sono rivelati alleati importanti per lo sviluppo di nuovi farmaci antivirali, in quanto questi ultimi possono inibire il ciclo vitale del virus interferendo con le attività delle proteine virali. La dimerizzazione del fattore di processività della DNA polimerasi, ppUL44, di HCMV è essenziale per il ciclo vitale del virus infatti necessaria per la replicazione del DNA virale mediata da oriLyt e può essere quindi considerata come un potenziale target terapeutico. Pertanto, in precedenza, tramite uno screening in silico sono state identificate 18 piccole molecole (Small Molecules, SMs) potenzialmente capaci di interferire con la omodimerizazzione di ppUL44. Saggi antivirali delle 18 SMs sul virus ricombinante . In questo lavoro sono riuscita a caratterizzare l’effetto di questi composti sulla viabilità e crescita cellulare, e quindi cominciare un’analisi preliminare del loro meccanismo di azione. Tutte hanno compromesso la replicazione dei virus reporter AD169 di HCMV ed una sua controparte resistente al GCV in maniera simile. Tra le 4 SMs scelte, B3, ha mostrato il Selectivity Index (SI) più alto e quindi l’unico composto ad essere ulteriormente analizzato. Siamo riusciti a dimostrare che B3 efficientemente inibisce lo strain virale AD169 di HCMV in saggi di Plaque Reduction (PRA). Come misurato tramite qPCR, B3 ha specificatamente inibito la sintesi del DNA virale a partire da 72 ore post infezione, come anche l’espressiIl nostro Gruppo di ricerca ha precedentemente identificato il proteoma nucleare di tutti i virus infettanti l’essere umano, distinguendo tra proteine virali che traslocano all’interno del nucleo della cellula infetta in modo IMPα/β1 dipendente o meno, combinando analisi bioinformatiche estese anche alla caratterizzazione funzionale delle sequenze di localizzazione nucleare (NLS) virali. Questo studio presenta l’opportunità senza precedenti di comparare la diversa interazione tra virus differenti con l’apparato di trasporto al nucleo della cellula infetta, con importanti implicazioni sullo sviluppo di nuovi target terapeutici antivirali a largo spettro. Una profonda analisi funzionale sui classici NLS (cNLS) putative identificati ci ha portato alla scoperta di più di 500 proteine codificanti cNLS. Siamo riusciti anche a fare una prima caratterizzazione del processo di import nucleare delle proteine Large T antigen (LTA) dei Polyomavirus (HPyV) e delle cNLS coinvolte. Nonostante i LT di 14 HPyV presentavano cNLS funzionali, queste erano molto diverse tra di loro sia in termini di struttura che di attività. Le attività delle cNLS hanno riflesso I livelli di accumulo nucleare delle proteine full-length, con l’attività più bassa associata alla cNLS di HPyV7. Nonostante molti HPyV codificano per una o più cNLS monopartite, 4 di esse presentavano cNLS bipartita. Chiaramente queste differenze strutturali influenzano affinità verso l’apparato IMPα/β1 dipendente ed il tropismo del virus. Inoltre, 2 tra le 26 cNLS con il punteggio di cNLS mapper più alto identificate con i nostri studi, sono altamente conservate e presentano vari ortologhi di due proteine, A19 e N2, della famiglia dei Poxivirdae. Entrambe le proteine localizzano nel nucleo della cellula ospite, in un pathway attivo IMPα/β1 dipendente, e la loro traslocazione nucleare viene inibita in presenza di mutazioni sito-specifico.  Human cytomegalovirus (HCMV) is a leading cause of severe diseases in immunocompromised individuals, including AIDS patients and transplant recipients, and in congenitally infected newborns. The utility of available drugs is limited by poor bioavailability, toxicity, and emergence of resistant strains. Therefore, it is crucial to identify new targets for therapeutic intervention. Among the latter, viral protein–protein interactions are becoming increasingly attractive. Since dimerization of HCMV DNA polymerase processivity factor ppUL44 plays an essential role in the viral life cycle, being required for oriLyt-dependent DNA replication, it can be considered a potential therapeutic target. We therefore previously performed an in silico screening and selected 18 small molecules (SMs) potentially interfering with ppUL44 homodimerization. Antiviral assays using recombinant HCMV TB4-UL83-YFP in the presence of the selected SMs led to the identification of four active compounds. In this work I have characterized the effect of such compounds on cell viability and growth and began a preliminary analysis of their mode of action. All of them impaired replication of an AD169-GFP reporter virus and its ganciclovir-resistant counterpart to a similar extend. Among the 4 selected SMs compound B3 exhibited the highest selectivity index (SI) and was further investigated. We could show that it also efficiently inhibited HCMV AD169 strain in plaque reduction assays (PRAs). As assessed by qPCR by Western blotting experiments, B3 specifically reduced viral DNA synthesis starting from 72 h post infection, consistent with the inhibition of viral gene expression starting from 48 h post infection by Western blotting experiments. Therefore, our data suggest that inhibition of ppUL44 dimerization could represent a new class of HCMV inhibitors, complementary to those targeting the DNA polymerase catalytic subunit or the viral terminase complex. Our research group previously defined the nuclear proteome of all human viruses, discriminating between viral proteins translocated in an IMPα/β1 dependent or independent process by combining bioinformatics analysis with extensive functional characterization of viral cNLSs. This study represents an unprecedented opportunity to compare how viruses differently interact with the host cell nuclear transport machinery, with important implications for the development of broad-range host targeted antivirals. In depth functional validation of identified putative classical nuclear localization signals (cNLSs) led to the discovery of more than 500 novel viral cNLS. We also report the first characterization of the nuclear import process of Human Polyomaviruses (HPyVs) Large T antigens (LT) as well as of the cNLS involved. Although LT from all 14 HPyVs bear a functional cNLS, the latter are extremely heterogenous, both in terms of activity and structural organization. Importantly, cNLS activity mirrored the levels of nuclear accumulation of full-length proteins, with lowest activity associated to HPyV7. Surprisingly, while most HPyVs bear one or more monopartite cNLS, four of them bear a bipartite cNLS. Clearly, such structural differences suggest an important role in conferring binding abilities to specific IMPα isoforms with potential implication for viral tropism determination. Furthermore, among the 26 top ranked cNLS based on cNLS mapper score, two extremely well conserved cNLS in orthologues of Vaccinia Virus proteins A19 and N2 were identified. Both proteins localized in the cell nucleus via energy and IMPα/β-dependent process, and their nuclear import could be abolished by site specific mutagenesis of the cNLSs, thus A19 and N2 mutant derivatives failed to localize in the nucleus

The weaponization of artificial intelligence (AI) and its implications on the security dilemma between states: could it create a situation similar to mutually assured destruction (MAD)

There is no a consensus in the IR literature on the possible implications of AI for cyber or nuclear capabilities, and whether AI would exacerbate, or potentially mitigate, the security dilemma between actors with varying capabilities. This capstone project explores these questions, using experts\u27 interviews and secondary data. It has tackled the issue under study by using the most-similar method in which most of the variables are similar. The paper argues the weaponization of AI exacerbates the security dilemma between states since it increases uncertainty. What is actually problematic about the military AI applications, as opposed to other military capabilities, is the declining role of humans. AI could be productive and counterproductive when it comes to policy making, implying the necessity of keeping humans over-the-loop. Neutralization makes AI deterrence reasonable for avoiding destructive, disruptive and manipulative outcomes. Like nuclear capabilities, establishing an AI-MAD structure, regulating the uses of AI and establishing a governing regime for AI arms race are the best possible policies. Keywords: Artificial Intelligence, Deterrence, Mutually Assured Destruction, Arms Contro

Asterinid seastars (Echinodermata: Asteroidea) from the Gulf of Oman, Iran

829-834Field surveys in the rocky south-east coast of Iran and northern part of the Gulf of Oman were conducted during a period from October 2014 to March 2015. The Asterinid seastars Patiriella paradoxa (Campbell and Rowe), Aquilonastra watersi (O’Loughlin and Rowe) and Aquilonastra iranica (Mortensen) are reported for the first time from the Iranian coast. The morphological taxonomy and the ecology of these asteroids are discussed in this work

PERANCANGAN USER INTERFACE DAN USER EXPERIENCE APLIKASI E-TICKET BUS NGURILING KOTA TASIK (NGULISIK) BERBASIS MOBILE DENGAN METODE DESIGN THINKING

Ngulisik adalah bus wisata di kabupaten tasikmalaya. Bus wisata ngulisik sendiri sudah mengatur tiketnya secara manual. Semakin pesatnya kemajuan teknologi informasi dan inovasi yang diadopsi dalam smartphone semakin memudahkan segala aktivitas manusia, seperti aplikasi e-ticket yang memudahkan masyarakat untuk memesan tiket hati. Perancangan aplikasi dimulai dengan desain desain antarmuka yang merupakan langkah awal implementasi ide, alur, dan cara kerja aplikasi yang dirancang pada akhirnya. Metode yang digunakan adalah design thinking. Metode design thinking terdiri dari emphatize, define, ideate, prototype dan test.Hasil uji desainer dengan 10 peserta menggunakan pertanyaan kemudahan tunggal untuk menguji kemudahan pengguna dengan hasil rank persentil tugas sebesar 89%, dan seq raw score sebesar 6.Ngulisik adalah bus wisata yang ada di daerah Kota Tasikmalaya. Bus wisata Ngulisik sendiri dalam mengelola tiketnya masih manual. Semakin pesatnya kemajuan teknologi informasi dan berbagai inovasi yang diterapkan dalam smartphone semakin memudahkan segala kegiatan manusia, contohnya seperti aplikasi e-ticket yang memudahkan masyarakat dalam memesan tiket sesuai keinginan. Perancangan aplikasi diawali dengan perancangan desain antarmuka yang merupakan langkah awal dalam implementasi ide, menata alur, dan cara kerja dari aplikasi yang nantinya dirancang. Metode yang dipakai adalah design thinking. Metode design thinking terdiri dari emphatize, define, ideate, prototype dan test . Hasil perancangan dilakukan test dengan 10 orang peserta dengan menggunakan perhitungan single ease question untuk menguji kemudahan pengguna dengan hasil task percentile rank yaitu 89%, dan SEQ raw score pada titik 6.2 dan system usability scale untuk menguji kepuasan pengguna dengan hasil rata-rata berdasarkan rumus SUS yaitu 91,5 termasuk kategori excellent dan grade scale B

Morphology and phylogeny of the sea anemone Stichodactyla haddoni (Cnidaria: Anthozoa: Actiniaria) from Chabahar Bay, Iran

Carpet anemones of the genus Stichodactyla are characterized by having no calcium carbonate skeleton, being flattened with rather short tentacles, being exclusively tropical, and being hosts for clown fish species. Most of the species belonging to this genus, however, are often very similar morphologically; thus, identification by external features is rather difficult. In this study, we have described the morphology and phylogenetic affinities of a carpet anemone species collected from Chabahar Bay. Although the Iranian species showed different coloration patterns within the same geographical area, they strongly resemble Stichodactyla haddoni Saville-Kent, 1893 in having short tentacles densely covering the undulated oral disc and white, pointed, recognizable exocoelic tentacles. Comparison of 18S rDNA with other actiniarians revealed that the 2 Iranian species are closely related to Stichodactyla haddoni, Stichodactyla gigantea, and Heteractis magnifica. This is the first record of Stichodactyla haddoni from the south eastern coast of Iran and the northern part of the Sea of Oman

Tinjauan Hukum Ekonomi Syariah Terhadap Pembayaran Jasa Transportasi Online Go-Jek Dengan Menggunakan Uang Elektronik Go-Pay Di Kota Cirebon

Gilan Priana, NIM: 1608202080, “TINJAUAN HUKUM EKONOMI SYARIAH TERHADAP PEMBAYARAN JASA TRANSPORTASI ONLINE GO-JEK DENGAN MENGGUNAKAN UANG ELEKTRONIK GO-PAY DI KOTA CIREBON” Go-Jek merupakan sebuah perusahaan yang menyediakan layanan jasa. Go-Jek memberikan inovasi kepada masyarakat dibidang jasa transportasi yaitu dengan memberikan layanan jasa ojek online. Banyak sekali layanan yang terdapat di dalam aplikasi Go-Jek. Seperti, Go-Ride, Go-Food, Go-Send, Go-Shop, dan Go-Car dan Go-Pay. Adapun permasalahan yang ada di penelitian ini yaitu pertama bagaimana cara sistem pembayaran dengan menggunakan uang elektronik Go-pay terhadap jasa transportasi online Go-jek, kedua Bagaimana tinjauan hukum ekonomi syariah terkait pembayaran yang mengguankan uang elektronik Go-pay terhadap jasa transportasi online Go-jek karena Dalam metode pembayaran Go-Jek dengan menggunakan Go-Pay sendiri banyak sekali perbedaan pendapat, Go-pay sendiri apakah dalam pemanfaatan Go-pay terhadap jasa transportasi Online ini sesuai dengan prinsip-prinsip akad yang telah diatur dalam Hukum Ekonomi Syariah atau justru lebih banyak mudaratnya bagi konsumen ataupun driver itu sendiri. Adapun tujuan penelitian ini adalah untuk mengetahui sistem pembayaran dengan menggunakan layanan Go-pay terhadap jasa transportasi online Go-jek, dan juga untuk Memahami pandangan hukum ekonomi syariah terkait pembayaran yang digunakan pada layanan Go-pay terhadap jasa transportasi online Go-jek. Kemudian Penelitian ini menggunakan cara penelitian kualitatif dengan pendekatan deskriptif, data yang dikumpulkan dengan cara observasi, wawancara, dan dokumentasi, kemudian semua data dianalisis dengan teknik deskriptif analisis. Adapun hasil dari penelitian ini yaitu pertama pengguna aplikasi Go-Jek bisa menggunakan dua macam cara pembayaran terhadap layanan yang ada di Go-Jek yaitu bisa dengan cara tunai atau memeberikan uang secara langsung maupun non tunai dengan cara memakai pembayaran lewat layanan Go-Pay. Dan jika ingin menggunakan layanan pembayaran dengan Go-Pay pengguna harus memiliki saldo yang mencukupi didalamnya. Dan yang kedua secara hukum ekonomi syariah ini merupakan Ijarah al Maushufah fi al Dzimmah atau suatu sewa jasa atas manfaat sesuatu dengan ketentuan rukun dan syarat ijarah dimana pelanggan adalah pihak penyewa dan Go-Jek adalah pihak yang disewa. Kata Kunci: Go-jek, Go-Pay, dan Hukum Ekonomi Syaria

PENGARUH PENERAPAN METODE ECLECTIC TERHADAP MOTIVASI BELAJAR SISWA PADA MATA PELAJARAN SEJARAH DI MTS AN-NUR JAGASATRU CIREBON

GILAN ILMAN HAVID : Mutu Pendidikan merupakan salah satu masalah yang kompleks karena melibatkan berbagai komponen dan dimensi yang saling memiliki ketergantungan satu dengan yang lainnya, mencakup konteks Pendidikan dan proses yang terus berkembang.Dalam konteks Pendidikan di Sekolah, Secara umum dapat dinyatakan bahwa kunci Pendidikan Nasional terlatak pada mutu Sekolah, dan kunci mutu Sekolah terletak pada mutu kegiatan Belajar Mengajar dengan berbagai macam metode pengajaran yang tepat guna, kemudian pada akhirnya diukur dari mutu hasil belajar yang dicapai siswa. Tujuan penelitian ini yakni untuk memperoleh gambaran atau data tentang Penerapan Metode Eclectic dalam meningkatkan Motivasi dan Hasil Belajar Siswa di MTs An-NUR Jagasatru Cirebon , Meneliti dan Menganalisa tentang Motivasi dan Hasil Belajar Siswa Pada Mata Pelajaran Sejarah dengan menggunakan Metode Eclectic dan yang tidak Menggunakan Metode Eclectic Peran Metode Pembelajaran sebagai faktor yang mempengaruhi Motivasi, dapat diamati dari lingkungan fisik dan lingkungan sosial yang mengitari siswa-siswi.Metode Pembelajaran juga menjadi pengaruh terhadap Motivasi dan Hasil Belajar Siswa Jenis penelitian yang digunakan yakni jenis penelitian kuantitatif. Pengumpulan data yang digunakan yakni Tes wawancara mendalam, observasi Angket dan dokumentasi. Analisis data yang digunakan yakni Pendekatan Teoritis dan Empiris yaitu data Penelitian yang diperoleh langsung melalui objek Penelitian yaitu Siswa Kelas VIII C Berdasarkan hasil penelitian menunjukan bahwa penerapan Metode Eclectic di kelas VIII C di MTs An-NUR Jagasatru Cirebon dikategorikan kuat dengan nilai rata-rata angket sebesar 47,62%. Adapun Motivasi Hasil Belajar Siswa di kelas VIII C MTs An-NUR Jagasatru Cirebon dikategorikan kuat dengan nilai rata-rata angket sebesar 58,73%. Hasil Penelitian uji hipotesis menunjukan bahwa antara penerapan Metode Eclectic terhadap Motivasi dan dan Hasil Belajar Siswa mempunyai pengaruh yang signifikan dan cukup kuat. Kata Kunci : Penerapan Metode, Eclectic, dan Meningkatkan Motivasi Belajar Sisw

A Miniaturized wide Stopband Low-pass Filter using T and Modified L Shapes Resonators

A new structure of microstrip-based low-pass filter with wide stopband and sharp roll-off is introduced, in this paper. In the proposed topology, resonators with T and modified L Shapes have been used. To improve the suppression factor and relative stopband bandwidth, the second resonator has been added to the first resonator. The designed filter has been fabricated on a 20 mm thickness RO4003 substrate, which has a loss tangent of 0.0021 and a relative dielectric constant equal to 3.38. All parameters including roll of rate, stopband, bandwidth, return loss, insertion loss, and figure of merit have significant coefficients. Simulation has been ran using advanced design system software. The 3dB cutoff frequency is appropriate. The value of the insertion loss parameter is <0.1 dB and the S11 parameter is −22 dB at this point. The stopband is extended from 2.42 up to 24 GHz, which shows an ultra-stopband. The results of the simulation and experiment are almost similar, which indicates a proper performance of the designed structure

Clinicopathologic Characteristics of Stomach Cancer among Patients Admitted to the Surgical Departments of Teaching Hospitals in Sana'a, Yemen

Objective: To describe the characteristics of stomach cancer among patients admitted to the surgical departments of teaching hospitals in Sana’a city, Yemen. Methods: This retrospective, descriptive study was conducted to identify the characteristics of stomach cancer among patients admitted to the surgical departments of two major teaching hospitals in Sana’a; namely, Kuwait University Hospital of Sana’a University and University of Science & Technology Hospital, in the period from January 2011 to June 2015. Sociodemographic and clinical data in addition to the characteristics of stomach cancer among 106 documented cases admitted over the study period were retrieved from the medical records and analyzed. Results: Of the stomach cancer patients admitted over the study period, 55.7% were males and 52.8% were aged 50–70 years old. The most frequent symptom was dyspepsia (96.2%) followed by weight loss (88.7%) and loss of appetite (81.1%). Dysphagia was present in 56.6% of the patients, while upper and lower gastrointestinal bleedings were present in 15.1% and 6.0% of the patients, respectively. Palpable masses were present among 35.8% of the patients, being most frequently observed in the pylorus and antrum (22.1%) and the body of the stomach (18.9%) as revealed by abdominal computed tomography. Regarding the histopathologic findings of endoscopic biopsies, tumors were well-differentiated in 32.1% and moderately or poorly differentiated in 26.4% of the patients each. However, moderately-to-poorly differentiated and lymphoma were less frequent (5.7%, each) and the gastrointestinal stromal tumor was observed in 1.9% of the patients. Conclusions: Clinicopathologic characteristics of stomach cancer among Yemeni patients are consistent with those documented internationally