Using Hidden Markov Models to Detect DNA Motifs

During the process of gene expression in eukaryotes, mRNA splicing is one of the key processes carried out by a complex called spliceosome. Spliceosome guarantees proper removal of introns and joining of exons before the translation process. Precise splicing is essential for the production of functional proteins. Spliceosome detects specific sequence motifs within an mRNA sequence called splice sites. Two of the splice sites are the 5’ and 3’ sites that border all the introns. Normal splicing process if disrupted by mutation may lead to fatal diseases. In this work, we predict splice sites in a human genome using hidden Markov models (HMMs). Prior to hidden Markov models, we tried to predict splice sites using higher order position weight matrices. Position Weight Matrix (PWM) is a conventional computational method used to represent splice sites or any sequence motif. In a set of aligned sequences, PWM captures the distribution of nucleotides at each position. The performance of simple PWMs in classifying authentic 5 and 3 splice sites and predicting cryptic splice sites in human genes is resonably well [1, 2, 3]. However, they are built by making a strong independence assumption between contiguous and non- contiguous nucleotide positions. Therefore, we developed a higher order PWM method that incorporates maximal dependence decomposition algorithm (MDD) [4] to successfully identify statistically significant splice sites. Simple PWM also fails to capture sites that lie in both splice site and non-splice site regions. Therefore, we implemented HMMs to overcome this limitation of PWM. We performed 10-fold cross validation of all the three methods for 5 and 3 authentic human splice sites from the HS3D database [5] and observed that MDD outperforms the other two methods with area under the Receiver Operating Characteristic curve (ROC) to be 0.96 and 0.93, respectively. Similarly, we performed classification of 5 and 3 putative cryptic splice sites in the beta-globin (HBB) and breast cancer type 1 susceptibility protein (BRCA1) genes. We observed that MDD performs very well in classifying both BRCA1 and HBB cryptic splice sites with area under ROC of 0.99, 0.95, 0.89 and 1.0 respectively. However, we also observed that HMMs perform fairly well in classifying splice sites and cryptic splice sites compared to traditional PWM method

In-Vitro Composite Surface Analysis Using Foru Polishing Systems A SEM STUDY

To evaluate the effect of four polishing methods on the surface gloss of a composite

Perencanaan Kebijakan Persediaan Vaksin Booster Dengan Metode Continuous Review (s,S) Untuk Mengurangi Overstock Di Rumah Sakit Tentara Kota Pematangsiantar

Pematangsiantar City Army Hospital is one of the state-owned health facilities that provides booster vaccination services with 4 types of booster vaccines available, namely sinovac, astrazeneca, pfizer and moderna. The uncertain level of demand for booster vaccines causes the Pematangsiantar City Army Hospital to require booster vaccine inventory policy planning using the continuous review (s,S) method to prevent overstock which results in considerable cost expenditures. From the calculation of booster vaccine inventory control using the continuous review method (s,S), it is obtained that the total inventory cost has a significant percentage change. For the type of sinovac, the percentage change in total inventory costs reaches 92% of the total inventory costs in the existing conditions, for astrazeneca reaches 58% of the total inventory costs in the existing conditions, for pfizer reaches 60% of the total inventory costs in the existing conditions, and for moderna reaches 95% of the total inventory costs in the existing conditions. The results of the calculation of the total cost of inventory with continuous review (s,S) can provide a decrease in costs incurred by the Pematangsiantar City Army Hospital. This is because the continuous review (s,S) inventory policy minimises the cost of vaccine shortages which are quite costly

Implementasi Metode Period Order Qantity Dalam Pengendalian Persediaan Bahan Baku Crude Palm Oil

PKS Pagar Merbau is a plantation company engaged in palm oil processing. Due to the unpredictable level of demand, determining the timing and number of orders becomes difficult, resulting in increased inventory costs. By using the Period Order Quantity Method, it aims to be able to control Crude Palm Oil raw material inventory which will minimize inventory costs. The Period Order Quantity (POQ) method is a development of the Economic Order Quantity (EOQ) method where the number of orders can minimize the total cost of inventory. The results of applying this method, obtained the optimal number of orders of 1,208,798.12 kg for one order with a frequency of 101 times a year with a safety stock of 3,000,200.61 kg and a reorder point of 3,961,816.26 kg. The total inventory cost according to company policy is  Rp. 3,159,298,770.65 while the total inventory cost according to the Period Order Quantity method is 2,879,961,532.42. Then the total inventory cost savings of Rp. 279,337,238.23 or 8.86

Il castello di carte. La transizione all’età adulta dei giovani Neet a Roma

Il contributo affronta il fenomeno della transizione all’età adulta dei giovani Neet (not in education, employment or training). Nel contesto italiano, disoccupazione, inattività e transizioni problematiche al lavoro sono strettamente legate al ritardo nella transizione all’età adulta e a modelli di dipendenza dalla famiglia. Lo studio mira a identificare modelli di transizione all’età adulta di Neet da una prospettiva biografica. È stata effettuata un’analisi qualitativa del contenuto computer-assistita su 32 interviste in profondità, che sono state condotte con Neet di età compresa tra i 25 e i 34 anni a Roma e nei suoi dintorni, nel quadro di un più ampio progetto di ricerca finanziato da Sapienza Università di Roma. Il contributo presenta una tipologia della transizione all’età adulta basata sulla posizione nella struttura familiare, le sequenze degli eventi nella biografia e il desiderio di autonomia. Nell’articolo vengono presentati sei tipi, caratterizzati in relazione al modello di dipendenza sviluppato, alle aspettative per il futuro e alle strategie soggettive, messe in atto per superare la condizione di Neet.The paper focuses on the transition to adulthood of young people not in education, employment or training (NEETs). In the Italian context, unemployment, inactivity and problematic transitions to work are strongly related to delayed transition to adulthood and patterns of dependency on family. Our study aims to identify pathways to adulthood of NEETs from a biographical perspective. We carry out a software-based qualitative content analysis on 32 in-depth interviews, which have been conducted with NEETs between 25 and 34 years old in Rome and its surroundings as a part of a research project founded by Sapienza University of Rome. An empirically grounded typology of transition to adulthood based on position in the household, biographical sequence of life events and subjective aspirations for autonomy is constructed and six types are presented and characterized regarding dependency patterns, expectations for the future and subjective strategies to leave NEET-condition

PENERAPAN ALGORITMA FLOYD-WARSHALL UNTUK OPTIMALISASI RUTE PENGANGKUTAN SAMPAH DI KECAMATAN BINJAI KOTA

Pengelolahan sampah harus semakin diperhatikan karena berhubungan dengan efisiensi biaya. Dengan optimasi transportasi sampah diharapkan pengangkutan sampah menjadi mudah, cepat, serta biaya relatif murah dengan tujuan akhir meminimalkan penumpukan sampah yang akan memberi dampak langsung bagi kesehatan masyarakat dan keindahan kota. Pada Kecamatan Binjai Kota rute pengangkutan sampah dilakukan secara acak sehingga menimbulkan biaya dan waktu yang tidak efisien. Pengangkutan sampah lebih optimal bila pengangkutan tersebut tidak memerlukan banyak waktu dan biaya. Penentuan lintasan terpendek untuk mempersingkat waktu dan biaya digunakan untuk menyelesaikan masalah pengangkutan sampah tersebut menggunakan Algoritma Floyd-Warshall. Setelah menyelesaikan tahapan Algoritma Floyd-Warshall dalam pengoptimalan rute pengangkutan sampah di Kecamatan Binjai Kota, jarak optimal yang dilalui oleh dump truck yaitu sebesar 13,27 km maka jarak yang ditempuh setiap bulannya adalah 398,1 km. Rute optimal yang dilalui yaitu V1 → V2 → V3 → V4 → V5 → V4 → V3 → V2 → V19 → V18 → V17 → V13 → V14 → V12 → V10 → V9 → V10 → V11 → V15 → V14 → V13 → V17 →18→ V19 → V20 → V21 → V22. Total biaya bahan bakar yang dikeluarkan Dinas selama ini Rp.1.545.000,- sebanyak 300 liter solar dalam sebulan dan setelah menggunakan Algoritma Floyd-Warshall bahan bakar yang dibutuhkan setiap bulan untuk rute tersebut adalah 132,7 liter dan biaya bahan bakar sebesar Rp.683.405,- dengan asumsi truk mematikan mesin saat mengangkut sampah. Penghematan bahan bakar sebanyak 167,3 liter dan biaya bahan bakar yang dihemat Rp.861.595,-. Hasil yang diperoleh menunjukan bahwa rute yang dibuat menggunakan Algoritma Floyd-Warshall menghasilkan rute dan biaya bahan bakar pengangkutan sampah yang lebih minimum

Development of Interactive Learning Based Discovery Learning to Improve Mathematic Representation and Self-Efficacy Abilities of MAN 1 Medan Students

Penelitian ini bertujuan untuk: 1) Menemukan pembelajaran interaktif berbasis discovery learning yang valid, praktis dan efektif dalam meningkatkan kemampuan representasi matematis dan self efficacy siswa; 2) Mendeskripsikan peningkatan kemampuan representasi matematis siswa dengan menggunakan pembelajaran interaktif berbasis discovery learning; 3) Mendeskripsikan peningkatan kemampuan self-efficacy siswa dengan menggunakan pembelajaran interaktif berbasis discovery learning. Penelitian ini merupakan penelitian pengembangan yang dilakukan dalam dua tahap, yaitu tahap pertama pengembangan pembelajaran interaktif melalui model pembelajaran discovery learning dengan menggunakan model pengembangan 4-D Thiagarajan dan tahap kedua mengujicobakan pembelajaran interaktif melalui model pembelajaran discovery learning yang dikembangkan di kelas X IIS 1 dan X IIS 2 MAN 1 Medan. Dari hasil uji coba I dan uji coba II diperoleh: 1) pembelajaran interaktif melalui model pembelajaran discovery learning yang dikembangkan telah memenuhi kriteria valid, praktis dan efektif ditinjau dari kriteria masing-masing; 2) pencapaian kemampuan representasi matematis siswa menggunakan perangkat pembelajaran dengan model pembelajaran discovery learning meningkat, ditinjau ketuntasan klasikal posttest uji coba I sebesar 68,75% meningkat menjadi 87,50% pada uji coba II; 3) kemampuan self efficacy siswa menggunakan perangkat pembelajaran dengan pendekatan model pembelajaran discovery learning meningkat, ditinjau dari ketuntasan klasikal posttest uji coba I sebesar 68,75% meningkat menjadi 87,50% pada uji coba II

Development of Contextual Teaching and Learning (CTL) Based Learning Devices to Improve Students’ Mathematic Problem Solving and Self Efficacy Ability in SMP Negeri 1 Hamparan Perak

This study aims to: 1) Find learning devices based on contextual teaching and learning (CTL) that can improve students' mathematic problem solving skills at SMP Negeri 1 Hamparan Perak; 2) Find learning devices based on contextual teaching and learning (CTL) that can increase student self-efficacy at SMP Negeri 1 Hamparan Perak; 3) Find practical contextual teaching and learning (CTL) based learning devices that can improve the problem solving and self-efficacy ability of students at SMP Negeri 1 Hamparan Perak; 4) Find learning devices based on contextual teaching and learning (CTL) that are effective to improve the problem-solving ability and mathematic self-efficacy of students at SMP Negeri 1 Hamparan Perak. The results show that: 1) Students' mathematic problem solving ability using learning devices based on contextual teaching and learning (CTL) increased; 2) The increase in students' self-efficacy after using contextual teaching and learning (CTL) based learning devices has increased; 3) The developed contextual teaching and learning (CTL) based learning device met the criteria for practicality of the learning devices; 4) The learning devices developed through contextual teaching and learning (CTL) to improve students' mathematics problem solving ability and self-efficacy have met the criteria of being effective. Keywords: development of learning devices, contextual teaching and learning, problem solving ability, self-efficacy DOI: 10.7176/JEP/12-8-07 Publication date:March 31st 2021

Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch.

Interleukin-2 (IL-2) is a small α-helical cytokine that regulates immune cell homeostasis through its recruitment to a high-affinity heterotrimeric receptor complex (IL-2Rα/IL-2Rβ/γc). IL-2 has been shown to have therapeutic efficacy for immune diseases by preferentially expanding distinct T cell compartments, and several regulatory T cell (Treg)-biasing anti-IL-2 antibodies have been developed for combination therapies. The conformational plasticity of IL-2 plays an important role in its biological actions by modulating the strength of receptor and drug interactions. Through an NMR analysis of milliseconds-timescale dynamics of free mouse IL-2 (mIL-2), we identify a global transition to a sparse conformation which is regulated by an α-helical capping "switch" at the loop between the A and B helices (AB loop). Binding to either an anti-mouse IL-2 monoclonal antibody (mAb) or a small molecule inhibitor near the loop induces a measurable response at the core of the structure, while locking the switch to a single conformation through a designed point mutation leads to a global quenching of core dynamics accompanied by a pronounced effect in mAb binding. By elucidating key details of the long-range allosteric communication between the receptor binding surfaces and the core of the IL-2 structure, our results offer a direct blueprint for designing precision therapeutics targeting a continuum of conformational states