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Kegiatan Pengabdian Kepada Masyarakat (PKM) ini diadakan di Desa Busung Kecamatan Sri Kuaola Lobam Kabupaten Bintan. PKM dilaksanakan dengan tujuan agar desa tersebut terlatih dan terampil dalam hal pembuatan Perdes dan memiliki produk Peraturan Desa tentang Pengelolaan Desa Wisata. Metode yang digunakan dalam kegiatan pengabdian Kepada masyarakat di Desa Busung dalam merumuskan peraturan Desa tentang Pengelolaan Desa Wisata ialah dengan cara partisipatif dalam perumusan naskah dasar peraturan desa. Waktu pelaksanaan dimulai bulan April sampai bulan November 2021.. Kegiatan PKM ini terbagi dalam 2 tahap, yaitu (1) survey dan identifikasi masalah, (2) Perumusan Rancangan Peraturan Desa. Selama PKM berlangsung, terjadi peningkatan kehadiran perangkat desa dan masyarakat yang terdiri dari Kepala Desa, BPD, Ketua RT, Ketua RW, tokoh masyarakat, dan pelau usaha yang antusias terlibat aktif memberikan saran tentang desa wisata yang ada di Desa Busung dan menambahkan kawasan dan wisata yang menarik yang ada di desa busung yang perlu dimasukkan draft Ranperdes Desa Wisata . Hal ini dapat dikatakan bahwa Perdes Desa wisata dibuat dengan melibatkan aspirasi masyarakat di desa mitra.

Para investor yang melakukan investasi dengan membeli saham di pasar modal akan menganalisis mengenai kondisi perusahaan terlebih dahulu agar investasi yang di lakukan dapat memberikan keuntungan. Dalam melakukan analisis akan saham ada banyak jenis analisis yang di lakukan terutama dalam hal membeli saham yang akan melakukan IPO itu sendiri. Keterbatasan informasi dalam analisis saham yang melakukan IPO ini sering terjadi yang dimana informasi ini sangat di butuhkan dalam menentukan keputusan nantinya. Penelitian ini memiliki tujuan untuk mengetahui pengaruh Ukuran Perusahaan dan Umur Perusahaan Terhadap harga saham perusahaan yang melakukan Initial Public Offering (IPO) sector keuagan. Penelitian ini menggunakan pendekatan kuantitatif. Pengambilan sampel menggunakan metode nonprobability sampling yang cara pengambilan sampelnya digunakan teknik sampling purposive. Data yang digunakan adalah data sekunder yang diperoleh dari laporan Perpektus Perusahaan yang melakukan IPO di Bursa Efek Indonesia. Analisis data yang digunkan dalam penelitian ini adalah analisis regresi linier berganda dan juga uji asumsi. Hasil penelitian ini menunjukkan bahwa pengaruah Ukuran Perusahaan berpengaruh secara Positif dan juga Signifikan terhadap Harga Saham dan Umur Perusahaan juga berpengaruh Secara Positif dan Signifikan Terhadap Harga saham.

Fiduciaire Eigendomsoverdracht atau lebih dikenal dengan sebutan Fiduciary Transfer of Ownership atau Fiduciary Security, adalah jenis keamanan yang sekarang telah digunakan oleh banyak orang dan tidak dapat dipungkiri pentingnya dalam dunia hukum privat. Dalam Jaminan Fidusia, objek akan yang tetap mengendalikan orang atau entitas yang memberikan jaminan fidusia atas objek (Penyedia Fidusia). Itulah sebabnya jaminan ini digunakan untuk memberikan penerima jaminan fidusia bentuk kepastian hukum dan untuk mengamankan pembayaran utang tertentu. Namun pada kenyataannya, masih ada banyak masalah mengenai hal ini seperti penerima fidusia yang tidak mendaftarkan objek di Kantor Pendaftaran Fidusia, atau juga kreditur menerima pelunasan dari pihak lain tanpa sepengetahuan pemberi fidusia, penyedia fidusia tidak membayar utangnya atau mereka mungkin telah menyewa atau mungkin menjual benda-benda tersebut. Dalam situasi ini, pemberi fidusia menghadapi kerugian. Penulis berfokus pada masalah di mana kreditur telah mengalihkan objek tersebut kepada pihak lain tanpa sepengetahuan pemberi fidusia dan perlindungan hukum apa yang dimiliki oleh pemberi fidusia mengenai situasi ini. Metode penelitian yang digunakan penulis adalah metode normatif. Hasil dari penelitian ini adalah untuk memberikan gambaran tentang perlindungan hukum preventif dan represif untuk pemberi fidusia sehubungan dengan penyedia fidusia atau kreditur telah mengalihkan atau menerima objek tanpa sepengetahuan pemberi fidusia

Telomeres, the ends of eukaryotic chromosomes, play pivotal roles in ageing and cancer and are targets of DNA damage and response. However, little is known about the structure and organization of telomeric chromatin at the molecular level. We used electron microscopy and single-molecule magnetic tweezers to characterize well-defined telomeric chromatin fibers of kilobasepair length. The cryo-EM structure of the compact telomeric tetranucleosome revealed a novel columnar folding, unusually short nucleosome repeat length of ∼132bp and the role of the histone N-terminal tails in stabilizing this structure. This is the first near-high resolution structure of chromatin with a native DNA sequence. The columnar structure exposes the DNA, making them susceptible to DNA damage. The telomeric tetranucleosome also exists in an alternative well-defined state, with one nucleosome open, accessible to protein factors. This suggests that protein factors, which plays a role in maintaining telomeres, can bind to telomeric chromatin in its compact heterochromatic form. The features of the telomeric chromatin structure reveals important insights of significant relevance for telomere function in vivo that provides information on mechanisms of nucleosome recognition by chromatin factors

The formulation in this research is how the personality influence, professionalism and experience teaching to the performance of teachers of the state of Tsanawiyah Madrasah 2 Mandailing Natal, and the purpose of this research is to know and analyze The influence of personality, professionalism and experience teaching to the performance of teachers of State Madrasah Tsanawiyah 2 Mandailing Natal. This research is a quantitative descriptive study. Data collection techniques are conducted through interviews, inquiry lists and documentation studies. The samples in this study were as many as 36 teachers. Variables are measured at Likert scale. Hypothesis testing using multiple linear regression analyses through F-test and T-Test. The results of the test in unison showed that the personality, professionalism and experience demonstrated a very noticeable influence on the performance of teachers of state Madrasah Tsanawiyah 2 Mandailing Natal with a value Fcount 24,804 Ftable 2.87 and significance value of 0.000b. Adjusted number of R Square by 0. 671 or (67.1%) indicates that the percentage of contribution of independent variable influence (personality, professionalism and teaching experience) to the dependent variable (teacher performance) amounted to 67.1%. Partially, personality positively affects the performance of Guru Madrasah Tsanawiyah Negeri 2 Mandailing Natal with a value of tcount ttable (2,988 2,028) and significance value of 0. 005. Professionalism positively and significantly influence the teacher's performance of state Madrasah Tsanawiyah 2 Mandailing Natal with a value of tcount ttable (2,728 2,028) and a significance value of 0. 010. The teaching experience has positive and significant effect on the teacher's performance of Negeri Tsanawiyah 2 Mandailing Natal with a value of tcount ttable (4,580 2,028) and a significance value of 0. 000. The highest value of a regression coefficient is the teaching Experience (X3) of 0. 532 or 53.2% and is the most dominant variable affecting the teacher's performance of Negeri 2 Mandailing Natal.

A global pandemic is underway caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 genome, like its predecessor SARS-CoV, contains open reading frames that encode accessory proteins involved in virus-host interactions active during infection and which likely contribute to pathogenesis. One of these accessory proteins is 7b (p7b), with only 44 and 43 residues in SARS-CoV and SAR-CoV-2, respectively. It has one predicted transmembrane domain fully conserved, which suggests a functional role, whereas most variability is contained in the predicted cytoplasmic C-terminus. In SARS-CoV, 7b protein is expressed in infected cells where the transmembrane domain was necessary and sufficient for Golgi localization. Also, anti-p7b antibodies have been found in the sera of SARS-CoV convalescent patients. In the present study, we have investigated the hypothesis that SARS-2 7b protein forms oligomers with ion channel activity. We show that 7b protein is almost completely α-helical in both SARS viruses and has a single transmembrane domain. In SDS, p7b forms various oligomers, from monomers to tetramers, but only monomers when exposed to reductants DTT or TCEP. Combination of SDS gel electrophoresis and and analytical ultracentrifugation (AUC) in both equilibrium and velocity modes suggests a dimer-tetramer equilibrium, and an equilibrium between monomeric, dimeric and tetrameric forms in the presence of reductant. Inclusion of pentamers or higher oligomers in the SARS-2 7b model worsened the fits. Although sensitivity to reductants suggests the involvement of disulfide-linked dimers, the presence of disulfide bonds was not essential to form tetramers. A preliminary model of this association was generated with Alpha-Fold, which was exposed to a molecular dynamics simulation in presence of a model lipid membrane. However, neither of the two models provide any evident pathway for ions. To confirm this, SARS-2 p7b was studied using Planar Bilayer Electrophysiology. Addition of p7b produced occasional membrane permeabilization that is not consistent with bona fide ion channels made of a tetrameric assembly of α-helices.

The orthorombicity of a crystal lattice structure is indicated by the difference in lattice parameter values ??a, b and c. This study aims to show that the split distance value between the angles of the diffraction peaks of the two planes (hkl) closest is the same as the orthorombicity value crystal structure on the GdBa2Cu3O7-? phase. For this purpose, in this study, a compound Gd0,85La0,15Ba2-xSrxCu3O7- has been synthesized with variations of x = 0.00, 0.05, 0.10, 0.20, 0.30 and 0.50. Samples were synthesized using a solid reaction method with wet mixing, sintered at a temperature of 900°C for 12 hours. From the results of XRD spectrum analysis with Match-3 and Rietica software, it is found that by the increasing the content of Sr the pattern of changes in the value of the split distance the angles of the diffraction peaks of (hkl) planes closest, the measurement and calculation results are the same with the changing pattern of the orthorombicity value. The measurement and calculation results, the split distance value between the diffraction peaks angle for the plane of (020) and (200) is almost equal to one-tenth of the orthorombicity value. Thus, the split distance value between the angles of the diffraction peaks of the two (hkl) planes closest can be used as an indicator of the orthorombicity a GdBa2Cu3O7-? phase crystal structure.

Hidroponik merupakan salah satu metode pertanian yang sering diterapkan oleh para petani modern saat ini. Metode ini memiliki banyak sekali keunggulannya, salah satunya dapat ditanam ditempat yang terbatas dan hanya membutuhkan media pertumbuhan dengan menggunakan air dan nutrisi. Akan tetapi ada satu aspek yang perlu di perhatikan dalam berhidroponik yaitu nutrisi yang dibutuhkan oleh tanaman. Nutrisi ini terdiri dari PH dan TDS. Kandungan ini sangatlah berpengaruh pada proses pertumbuhan tanaman, maka dari itu ada besaran idealnya agar tanaman bias tumbuh secara maksimal. Untuk kandungan PH sekitar 5,5 – 6,5 PH dan TDS sekitar 1050 – 1200 PPM. Maka dari itu penulis membuat suatu alat yang bias mengatur kandungan TDS dan PH secara otomatis menggunakan metode fuzzy logic agar didapat besaran TDS dan PH yang ideal.Hasil yang didapatkan pada saat pengujian, fuzzy logic dapat berfungsi dengan menghasilkan pengukuran pada sensor PH yang memiliki error sekitar 4,83% dari nilai 5,5 – 6,5. Sedangkan untuk untuk pengujian sensor TDS memiliki error sebesar 8,29% dari nilai 1050 – 1200 ppm

Lipid membranes play an essential role in biology, acting as host matrices for biomolecules like proteins and facilitating their functions. Their structures, and structural responses to physiologically relevant interactions, i.e. with membrane proteins, provide key information for understanding biophysical mechanisms. Hence, there is a crucial need of methods to understand the effects of membrane host molecules on the lipid bilayer structure. Here, we present a purely experimental method for obtaining the absolute scattering length density (SLD) profile and the area per lipid of liposomal bilayers, by aiding the analysis of small angle X-ray scattering (SAXS) data with the volume of bare headgroups obtained from fast (20-120s) grazing incidence off-specular scattering (GIXOS) data from monolayers of the same model membrane lipid composition. The GIXOS data experimentally demonstrate that the variation of the bare headgroup volume upon lipid packing density change is small enough to allow its usage as a reference value without knowing the lipid packing stage in a bilayer. This approach also bares the advantage that the reference volume is obtained at the same aqueous environment as used for the model membrane bilayers. We demonstrate the validity of this method using several typical membrane compositions, as well as one example of a phospholipid membrane with an incorporated transmembrane peptide. This methodology allows to obtain absolute scale values rather than relative scale by using solely X-ray-based instrumentation, retaining a similar resolution of SAXS experiments. The presented method has high potential to understand structural effects of membrane proteins on the biomembrane structure.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. In SARS-CoV-2, the channel-forming envelope (E) protein is almost identical to the E protein in SARS-CoV, and both share an identical α-helical channel-forming domain. Structures for the latter are available in both detergent and lipid membranes. However, models of the extramembrane domains have only been obtained from solution NMR in detergents, and show no β-strands, in contrast to secondary-structure predictions. Herein, we have studied the conformation of purified SARS-CoV-2 E protein in lipid bilayers that mimic the composition of ER-Golgi intermediate compartment (ERGIC) membranes. The full-length E protein at high protein-to-lipid ratios produced a clear shoulder at 1635 cm-1, consistent with the β-structure, but this was absent when the E protein was diluted, which instead showed a band at around 1688 cm-1, usually assigned to β-turns. The results were similar with a mixture of POPC:POPG (2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine/3-glycerol) and also when using an E-truncated form (residues 8-65). However, the latter only showed β-structure formation at the highest concentration tested, while having a weaker oligomerization tendency in detergents than in full-length E protein. Therefore, we conclude that E monomer-monomer interaction triggers formation of the β-structure from an undefined structure (possibly β-turns) in at least about 15 residues located at the C-terminal extramembrane domain. Due to its proximity to the channel, this β-structure domain could modulate channel activity or modify membrane structure at the time of virion formation inside the cell. Ministry of Education (MOE) Published version This research and the APC were funded by grants awarded to J.T. by the Singapore Ministry of Education (MOE), Tier 1 grant number RG92/21.

In an effort to explore the use of natural resources, stoneware ceramics have been made using iron sand as a filler to replace quartz Kalimantan. The results showed that iron sand can be well used in making stoneware ceramics. This is shown by the measurement of water absorption which is less than 5% and has compressive strength slightly smaller compared to stoneware ceramics made with quartz as a filler.

As social beings, social relations are fundamental and inseparable. Social interaction that has many differences requires the existence of a specific guidance or law adopted by the community. The law is for the sake of realizing a sense of security and assured in establishing community relations, as well as to realize a good social relationship, harmonious and without having to harm others. A specific form of guidance in society is the agreement. Indonesia has three sub-systems of law that are broadly divided into namely western law, customary law, and Islamic law. The procurement of agreements in order to increase security and certainty is already inevitable in the modern era, which is rapidly growing as it is today. Therefore, before entering into an agreement, it is necessary to comply with all conditions of the validity of the agreement in order for the agreement to become valid as a law so that the purpose of the agreement can be reached. One of the terms of the validity of the treaty that is "lawful cause" is an important thing to be studied deeply by the parties who make the contract because of the difference of the legal system in its environment (Indonesia) is mainly the conventional agreement system which is used as the standard of legislation in Indonesia and the system Islamic agreement or sharia that is used as the guidance of the majority of Indonesian people who are Muslims, so that there are no things that do not want inflicted in the future

Keothorhombikan suatu struktur kisi kristal ditunjukkan oleh adanya perbedaan nilai parameter kisi a, b dan c. Penelitian ini bertujuan untuk menunjukkan bahwa nilai jarak pisah antara sudut puncak difraksi kedua bidang (hkl) yang paling dekat sama dengan nilai orthorhombisitas struktur kristal pada fase GdBa2Cu3O7-?. Untuk tujuan tersebut, dalam penelitian ini telah disintesis senyawa Gd0,85La0,15Ba2-xSrxCu3O7-dengan variasi x = 0,00, 0,05, 0,10, 0,20, 0,30 dan 0,50. Sampel disintesis menggunakan metode reaksi padatan dengan pencampuran basah, disintering pada suhu 900°C selama 12 jam. Dari hasil analisis spektrum XRD dengan software Match-3 dan Rietica didapatkan bahwa, dengan bertambahnya kandungan Sr pola perubahan nilai jarak pisah sudut puncak difraksi bidang (hkl) terdekat hasil pengukuran dan perhitungan sama dengan pola perubahan nilai keorthorhombikan. Hasil pengukuran dan perhitungan nilai jarak pisah antara sudut puncak difraksi untuk bidang (020) dan (200) hampir sama dengan sepersepuluh dari nilai keorthorhombikan. Dengan demikian, nilai jarak pisah antara sudut puncak difraksi dari dua bidang (hkl) terdekat dapat digunakan sebagai indikator keorthorhombikan struktur kristal fase GdBa2Cu3O7-?.

This study is carried out to improve matching accuracy between level 1 feature and level 2 feature of a fingerprint by applying feedback mechanism. Level 1 feature consists of ridge frequency and orientation while level 2 feature consists of minutia point coordinate and orientation. The matching accuracy of level 1 feature slightly lower compared with level 2 feature and the accuracy even higher when applying feedback mechanism. The toddler fingerprint image that used in this study consist of 400 images from 7 toddlers that obtained by the author. The matching accuracy of level 2 feature improved approximately around 18.6% when both feedback mechanism employed, and 14.5% without feedback mechanism on both sides compared to level 1 feature accuracy.

Prediksi beban listrik memiliki hubungan yang erat dengan penempatan dan pengembangan gardu induk sebagai langkah balancing load capacity . Diperlukan prediksi konsumsi beban listrik secara tepat untuk dapat memberikan rekomendasi penempatan gardu induk sesuai pusat beban yang ada. Salah satu langkah awal adalah dengan mempertimbangkan analisis komponen spasial dalam peramalannya. Pada penelitian ini, pusat beban; topografi; demografi; geologi serta peta seismotektonik akan menjadi variabel atribut yang diolah dalam analisis peramalan spasial. Dengan adanya area pengelompokan pusat beban menurut tingkat konsumsi listrik masa depannya maka dapat dilakukan evaluasi penempatan gardu induk disesuaikan dengan kondisi konsumsi masing-masing daerah amatan. Untuk pengoptimalan penempatan gardu induk yang dilakukan, Rencana Tata Ruang Wilayah (RTRW) juga menjadi hal yang harus dipertimbangkan. Langkah tersebut dilakukan sebagai bentuk langkah strategik perusahaan dalam menyikapi dinamika ketidakpastian beban. Sehingga dalam penelitian ini, peneliti bertujuan untuk menganalisis lokasi penempatan gardu induk yang optimal dengan mempertimbangkan atribut dan interaksi spasial yang mengacu pada pusat beban /konsumsi beban listrik masa depan yang dilakukan dengan menggunakan metode Spatial Multicriteria Decision Analysis melalui perantara software ArcGIS ( Geographic Information System ). Pemilihan lokasi berdasarkan prinsip kriteria kecocokan menggunakan metode WLC ( Weighted Linier Combination ). Sedangkan untuk peringkat skor dan pembobotan faktor pada peta dianalisis dengan AHP ( Analytic Hierarchy Process ). Peta gabungan yang berisi prioritas lokasi potensial akan diwakili oleh beberapa poligon yang diperoleh dari analisis spatial MCDA pada software ArcGIS 10.1. Beberapa lokasi gardu induk yang optimal di area Jawa Timur dipilih sebagai lokasi kandidat setelah menghilangkan lokasi dengan nilai terendah melalui AHP pada software Expert Choice . Lokasi-lokasi tersebut di rangking untuk mendapatkan lokasi yang diinginkan.

Immunization and vaccination are very important for infant and toddler. The management system for registration in formal institution is not built yet. To overcome this problem, infant and toddler recognition using fingerprint can be chosen to identify infant and toddler. In this paper, we proposed a telebiometric system for infant and toddler recognition. The proposed system has three main components, namely sensor, mobile phone or PC, and server. The system used some feature extraction methods, such as ridge period, singular point, and minutiae, as fingerprint features to match it with the database data. The result showed that the system has 0.82 accuracy and 321 ms average running time.

Coronaviruses (CoV) cause common colds in humans, but are also responsible for the recent Severe Acute, and Middle East, respiratory syndromes (SARS and MERS, respectively). A promising approach for prevention are live attenuated vaccines (LAVs), some of which target the envelope (E) protein, which is a small membrane protein that forms ion channels. Unfortunately, detailed structural information is still limited for SARS-CoV E, and non-existent for other CoV E proteins. Herein, we report a structural model of a SARS-CoV E construct in LMPG micelles with, for the first time, unequivocal intermolecular NOEs. The model corresponding to the detergent-embedded region is consistent with previously obtained orientational restraints obtained in lipid bilayers and in vivo escape mutants. The C-terminal domain is mostly α-helical, and extramembrane intermolecular NOEs suggest interactions that may affect the TM channel conformation., Graphical abstract Unlabelled Image, Highlights • SARS-CoV E protein is a pentameric ion channel. • The SARS-CoV E protein (8–65) is almost completely α-helical in LMPG micelles. • Ten inter-monomeric NOEs have been identified. • The SARS-CoV E protein (8–65) pentameric model has been obtained. • Orientation of key residues, e.g. Val25 is consistent with previous in vivo results.

Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity. Published version

Highlights • The envelope protein of MERS coronavirus (MERS-CoV E protein) has been purified. • MERS-CoV E protein forms pentameric ion channels. • MERS-CoV E protein has one transmembrane domain. • The full length construct obtained is amenable to structural determination by NMR in detergents., The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly identified pathogen able of human transmission that causes a mortality of almost 40%. As in the case of SARS-CoV, MERS virus lacking E protein represents a potential vaccine. In both cases, abolishment of channel activity may be a contributor to the attenuation observed in E-deleted viruses. Herein, we report that purified MERS-CoV E protein, like SARS-CoV E protein, is almost fully α-helical, has a single α-helical transmembrane domain, and forms pentameric ion channels in lipid bilayers. Based on these similarities, and the proposed involvement of channel activity as virulence factor in SARS-CoV E protein, MERS-CoV E protein may constitute a potential drug target.

Shoreline is a boundary area between land and sea, where there are few phenomena that unique and dynamic. This phenomenon includes abrasion erosion and sedimentation. Development of infrastructure and reclamation is human action that can alter the ecosystem as well as the order of the shoreline. Observation shoreline is a field that is very useful for Indonesia because Indonesia is an archipelagic country consisting of many islands. Danger from the sea could come at any time and could be very dangerous for human life, so it is important to observe, to monitor and to maintain the shoreline. This study used Support Vector Machine (SVM) as classification method, and Principal Component Analysis of the band images and Histogram of Oriented Gradient as feature extraction for shape features. Multi temporal Landsat will be consist of Landsat 5 acquired in 1996 and Landsat 8 acquired in 2016. The result of this study shown that 85% of shoreline in 2016 changed after applied image enhancement compared to shoreline in year of 1996.

One important aspect of the financial statements is timeliness. Financial reports presented on a timely basis can reduce the occurrence of information asymmetry, then will reduce the impact of the conflict of interest between agents and principals. This is because the financial statements are information that becomes the principal consideration in decision making. Based on the theory and the results of previous research, several factors that can affect the timeliness of financial statement submission is profitability and firm size. However, both of these factors may not affect the timeliness of the delivery of financial statements due to contingency factors, so a moderator is needed to reconcile the conflicting results, ie, an audit opinion. Therefore, this study aims to determine the effect of profitability and firm size on the timeliness of financial reporting with audit opinion as a moderator variable. This research was conducted on manufacturing companies in 2012-2015 in the Indonesia Stock Exchange. Samples taken as many as 88 manufacturing companies, determined by purposive sampling method. Data was collected using non-participant observation. Analysis technique used is the Logistic Regression Analysis by using Moderated Regression Analysis. Based on the analysis concluded that profitability has no effect on the timeliness of financial reporting, firm size have a positive effect on the timeliness of financial reporting, audit opinion is able to moderate the influence of profitability on the timeliness of financial reporting, and audit opinion is not able to moderate the influence of firm size on the timeliness of financial reporting.

The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH protein has a single α-helical transmembrane (TM) domain that forms pentameric ion channels. Herein, we report the first inhibitor of the SH protein channel, pyronin B, and we have mapped its binding site to a conserved surface of the RSV SH pentamer, at the C-terminal end of the transmembrane domain. The validity of the SH protein structural model used has been confirmed by using a bicellar membrane-mimicking environment. However, in bicelles the α-helical stretch of the TM domain extends up to His-51, and by comparison with previous models both His-22 and His-51 adopt an interhelical/lumenal orientation relative to the channel pore. Neither His residue was found to be essential for channel activity although His-51 protonation reduced channel activity at low pH, with His-22 adopting a more structural role. The latter results are in contrast with previous patch clamp data showing channel activation at low pH, which could not be reproduced in the present work. Overall, these results establish a solid ground for future drug development targeting this important viroporin. IMPORTANCE The human respiratory syncytial virus (hRSV) is responsible for 64 million reported cases of infection and 160,000 deaths each year. Lack of adequate antivirals fuels the search for new targets for treatment. The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by hRSV and other paramyxoviruses, and its absence leads to viral attenuation in vivo and early apoptosis in infected cells. SH protein forms pentameric ion channels that may constitute novel drug targets, but no inhibitor for this channel activity has been reported so far. A small-molecule inhibitor, pyronin B, can reduce SH channel activity, and its likely binding site on the SH protein channel has been identified. Black lipid membrane (BLM) experiments confirm that protonation of both histidine residues reduces stability and channel activity. These results contrast with previous patch clamp data that showed low-pH activation, which we have not been able to reproduce.

Coronavirus envelope (CoV E) proteins are ∼100-residue polypeptides with at least one channel-forming α-helical transmembrane (TM) domain. The extramembrane C-terminal tail contains a completely conserved proline, at the center of a predicted β-coil-β motif. This hydrophobic motif has been reported to constitute a Golgi-targeting signal or a second TM domain. However, no structural data for this or other extramembrane domains in CoV E proteins is available. Herein, we show that the E protein in the severe acute respiratory syndrome virus has only one TM domain in micelles, whereas the predicted β-coil-β motif forms a short membrane-bound α-helix connected by a disordered loop to the TM domain. However, complementary results suggest that this motif is potentially poised for conformational change or in dynamic exchange with other conformations. Accepted version

It has been shown previously in the severe acute respiratory syndrome coronavirus (SARS-CoV) that two point mutations, N15A and V25F, in the transmembrane domain (TMD) of the envelope (E) protein abolished channel activity and led to in vivo attenuation. Pathogenicity was recovered in mutants that also regained E protein channel activity. In particular, V25F was rapidly compensated by changes at multiple V25F-facing TMD residues located on a neighboring monomer, consistent with a recovery of oligomerization. Here, we show using infected cells that the same mutations, T16A and A26F, in the gamma-CoV infectious bronchitis virus (IBV) lead to, in principle, similar results. However, IBV E A26F did not abolish oligomer formation and was compensated by mutations at N- and C-terminal extramembrane domains (EMDs). The C-terminal EMD mutations clustered along an insertion sequence specific to gamma-CoVs. Nuclear magnetic resonance data are consistent with the presence of only one TMD in IBV E, suggesting that recovery of channel activity and fitness in these IBV E revertant mutants is through an allosteric interaction between EMDs and TMD. The present results are important for the development of IBV live attenuated vaccines when channel-inactivating mutations are introduced in the E protein. IMPORTANCE The ion channel activity of SARS-CoV E protein is a determinant of virulence, and abolishment of channel activity leads to viral attenuation. E deletion may be a strategy for generating live attenuated vaccines but can trigger undesirable compensatory mechanisms through modifications of other viral proteins to regain virulence. Therefore, a more suitable approach may be to introduce small but critical attenuating mutations. For this, the stability of attenuating mutations should be examined to understand the mechanisms of reversion. Here, we show that channel-inactivating mutations of the avian infectious bronchitis virus E protein introduced in a recombinant virus system are deficient in viral release and fitness and that revertant mutations also restored channel activity. Unexpectedly, most of the revertant mutations appeared at extramembrane domains, particularly along an insertion specific for gammacoronaviruses. Our structural data propose a single transmembrane domain in IBV E, suggesting an allosteric interaction between extramembrane and transmembrane domains.