bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementasi Kurikulum Muatan Lokal dalam Mencapai Target Hafalan Al-Qur’an 4 Juz di SD Islam Annajah Jakarta Barat
Authors: Fatimah  , Sri Tuti Rahmawati
Published: July 2021

Many problems faced by the memorizers of the Qur'an such as not being able to memorize correctly according to makhraj and tajwid, there are still many students who have not memorized it perfectly, lack of dividing time in rote repetition, not focus on memorization, That is why it is not easy to memorize the Qur'an.  This study aims to determine and describe how the concepts, implementation, evaluation and inhibiting and supporting factors in the Implementation of Local Content Curriculum in achieving the target of memorizing Al-Qur'an 4 juz at SD Islam Annajah West Jakarta. The object of this research is the Principal, Chairperson of the Tahfiz Coordinator, Tahfiz Teachers and students SD Islamic Annajah West Jakarta. Data collection techniques used are interviews, observation and documentation. The steps taken are data reduction, data presentation and conclusion  drawing. The results of this study indicate that: (1) The concept of the Tahfiz Al-Qur'an Local Content Curriculum in class I is that students are focused on learning to read the Qur'an and memorizing the surah-An-Nas to Al-Fil, class II is memorizing Al-Qur'an juz 30, class III is memorizing Al-Qur'an juz 29, class IV is memorizing Al-Qur'an juz 28, class V is me-morizing Al-Qur'an juz 27 and for class 6 repeating all memorization from juz 27-30. (2) The implementation of tahfidz is conducted every Monday-Friday. Before students add new memorization ustad / ustadzah recite the verse first, After that students follow together. For students who have memorized it directly deposit the memorization one by one. (3) The evaluation is carried out in several stages in 1 year, namely PTS 1, PAS 1 and PTS 2, PAT 2. Exams are conducted for 3 days, namely Monday, Tuesday and Wednesday. (4) Supporting factors in implementing this program are age, teacher criteria, motivation from parents and teachers, facilities and infrastructure. While the inhibiting factors in implementing the tahfidz program are students, lack of time management, and forgetfulness.
HUBUNGAN PEMBERIAN STIMULASI DENGAN PERKEMBANGAN BALITA USIA 1-5 TAHUN DI POSYANDU SERUNAI VII KELURAHAN VI SUKU WILAYAH KERJA PUSKESMAS TANAH GARAM KOTA SOLOK
Authors: Afridon Afridon
Published: July 2021

Factors affecting growth and development are genetic, environmental (prenatal, and post natal), post-natal environments that affect children's growth and development in general can be classified as biological environments. One factor that influences development is stimulation. The type of research used is descriptive analytic with Cross Sectional Study design in which to see the relationship between two variables. The variable in this study is the independent variable is the provision of stimulation and the dependent variable is the development of toddlers aged 1-5 years. Based on the results of research conducted on 34 respondents, it is known that more than a portion (64.7%) of respondents provide developmental stimulation in infants, more than a portion (61.8%) of infants of respondents have appropriate development and analysis results between the provision of stimulation and development under-five children were found to be more than a part (66.7%) who did not provide stimulation that experienced dubious development. While statistically obtained p value = 0.025 ˂ 0.05, which means that there is a significant relationship between those who do not provide stimulation with the development of children who have doubts. It is expected that health workers provide information on how to provide stimulus to their toddlers in accordance with the stage of development of their age so that respondents are able to provide stimulus to their children.
MENINGKATKAN KEMAMPUAN MENYELESAIKAN SOAL CERITA MATEMATIKA SISWA KELAS V UPT. SD NEGERI 16 SARUASO MELALUI MODEL PEMBELAJARAN CREATIVE PROBLEM SOLVING
Authors: Yurnailis Yurnailis
Published: July 2021

Penelitian ini bertujuan untuk meningkatkan kemampuan menyelesaikan soal cerita matematika siswa kelas V UPT. SD Negeri 16 Saruaso melalui model pembelajaran Creative Problem Solving. Jenis penelitian ini adalah Penelitian Tindakan Kelas. Subjek penelitian adalah siswa kelas V UPT. SD Negeri 16 Saruaso yang berjumlah 18 siswa, terdiri dari 10 siswa putra dan 8 siswa putri. Objek penelitian adalah kemampuan menyelesaikan soal cerita matematika. Data hasil penelitian diperoleh dari observasi dan tes hasil belajar. Data yang diperoleh dianalisis secara deskriptif kuantitatif dan deskriptif kualitatif. Adapun kriteria keberhasilan penelitian tersebut ditandai dengan perolehan nilai rata-rata kelas ≥ 75 dan minimal 75% dari jumlah siswa mencapai KKM (75). Hasil penelitian menunjukkan bahwa penggunaan model pembelajaran Creative Problem Solving dapat meningkatkan kemampuan menyelesaikan soal cerita matematika siswa kelas V UPT. SD Negeri 16 Saruaso. Peningkatan kemampuan menyelesaikan soal cerita matematika ditunjukkan oleh hasil tes. Pada pra tindakan terdapat 44,44% (8 siswa) dari jumlah 18 siswa yang mencapai KKM. Hasil tes pada siklus 1 menunjukkan ada 72,22% (13 siswa) dari jumlah siswa yang mencapai KKM, sedangkan pada siklus 2 terdapat 88,89% (16 siswa) dari jumlah siswa yang mencapai KKM. Nilai rata-rata sebelum siklus sebesar 63,33, sedangkan pada akhir siklus 1 nilai rata-rata tes sebesar 74,44, dan pada akhir siklus 2 sebesar 80.
PENINGKATAN KEMAMPUAN MEMBACA PERMULAAN MELALUI MEDIA BIG BOOK SISWA KELAS IA SD NEGERI 04 JAHO
Authors: Daswati Daswati
Published: July 2021

Penelitian ini bertujuan untuk: (1) meningkatkan proses pembelajaran membaca permulaan melalui media big book, dan (2) mendeskripsikan peningkatan kemampuan membaca permulaan melalui media big book pada siswa kelas IA SD Negeri 04 Jaho Kecamatan X Koto Kabupaten Tanah Datar. Penelitian ini merupakan penelitian tindakan kelas dengan model Kemmis dan Mc Taggart. Subyek penelitian adalah siswa kelas IA SD Negeri 04 Jaho Kecamatan X Koto Kabupaten Tanah Datar yang berjumlah 12 siswa. Teknik pengumpulan data pada penelitian ini menggunakan teknik observasi, catatan lapangan dan tes. Instrumen penelitian yang digunakan yaitu lembar pedoman observasi rating berskala dan tes unjuk kerja membaca permulaan. Teknik analisis data yang digunakan pada penelitian ini adalah deskriptif kualitatif dan deskriptif kuantitatif. Hasil penelitian menunjukkan bahwa penggunaan media big book dapat meningkatkan kemampuan membaca permulaan siswa kelas IA SD Negeri 04 Jaho Kecamatan X Koto Kabupaten Tanah Datar dari segi proses maupun hasil. Penggunaan media big book dalam pembelajaran membaca permulaan diawali dengan mengajak siswa untuk memprediksi isi cerita berdasarkan pengamatan terhadap gambar ilustrasi pada halaman sampul. Prediksi siswa tersebut ditulis di papan tulis. Guru membacakan big book dengan intonasi dan lafal yang tepat serta menunjuk setiap kata yang dibaca. Melalui pemodelan ini, siswa terdorong untuk mampu membaca seperti yang dicontohkan oleh guru. Setelah itu, guru mencocokkan prediksi siswa dengan isi cerita. Siswa dipersilakan untuk menyampaikan kesan atau tanggapannya. Guru membacakan sekali lagi sebelum siswa membaca secara individu di depan kelas. Guru membimbing siswa dalam membaca dan memberikan motivasi setelah siswa selesai membaca di depan kelas. Dari segi hasil, peningkatan dibuktikan dengan nilai rata-rata kemampuan membaca permulaan pada pratindakan 62,38 meningkat menjadi 67,22 pada siklus I dan 78,66 pada siklus II. Persentase pencapaian kriteria keberhasilan mengalami peningkatan pada pratindakan sebesar 17,24% meningkat menjadi 34,48% pada siklus I dan 79,31% pada siklus II.
KAJIAN UPAH PEKERJA KONSTRUKSI PADA PROYEK BANGUNAN GEDUNG DI PROVINSI SUMATERA BARAT
Authors: Herista Febrimen , Yusman Ana Susanti
Published: July 2021

In the world of the construction industry, the wages of workers are quite large, which is about one-third of the construction value. So the company should pay serious attention to the wages of these workers. However, information regarding the wages of construction workers is only in the form of daily wages for casual workers and monthly wages for permanent workers, while information on the cost of workers' costs is not available. This study aims to identify the components of labor costs and their proportion to the overall cost of construction workers wages and to identify factors related to wages and costs of construction workers. In this study the method used is empirical and inductive methods, then the data obtained is processed and analyzed using descriptive statistics and comparative analysis. To model the burden of labor costs into its components and their respective proportions, descriptive statistical methods are used, while to analyze the variables -variables that affect wages and costs of workers used comparative analysis method. From the results of data processing, conclusions are drawn using the inductive method as follows: 1) The costs of workers are grouped into direct and indirect costs, and conditional costs, but the distribution of each cost component between permanent workers and freelancers is different; 2) Company profile, project profile, and worker profile. have an effect on wages and costs of construction workers.
SIFAT KEPUTUSAN BADAN PENGAWAS PEMILIHAN UMUM DALAM PENYELESAIAN SENGKETA PEMILIHAN UMUM
Authors: Siratni Mia
Published: July 2021

Bawaslu resolves by deliberation by bringing together the disputing parties to then take a final and binding decision. The final and binding nature of this Bawaslu decision does not apply to certain disputes, namely the dispute over the verification of political parties participating in the General Election and the determination of the final list of candidates for the election of members of the DPR, DPD, and DPRD. The existence of these two characteristics of Bawaslu's decision then led to different interpretations between Bawaslu and the KPU. The formulation of the problem, namely 1). The authority of Bawaslu in resolving election disputes regarding the task of supervising the implementation of elections, 2). The nature of Bawaslu's decisions in resolving election disputes. The research method used in this paper is normative juridical, namely an approach to legal norms or applicable laws and regulations, theories, and history. From the discussion of the problem, it is concluded that a decision that is final and binding is given to Bawaslu by law in order to end election disputes so that it will show the role of Bawaslu as a unified function of organizing elections. Meanwhile, exceptions to the nature of final and binding decisions on political party verification disputes and the permanent list of candidates for members of the DPR, DPD, and DPRD indicate that Bawaslu is not a judicial institution, so it cannot decide disputes related to constitutional rights as election participants.
URGENSI PENGATURAN PENGEMBANGAN ENERGI TERBARUKAN SEBAGAI WUJUD MENDUKUNG KETAHANAN ENERGI NASIONAL
Authors: Faisal Faisal
Published: July 2021

Energy sovereignty in Indonesia is experiencing problems with a decline in national energy security. Indonesia's energy system is currently facing serious challenges. The imbalance in the condition of energy supplies with national energy needs, especially the oil and gas sector and efforts to fulfill national energy needs in a sustainable manner are the main problems of this nation in the energy sector. It is absolutely necessary to have strategic efforts in the field of creating new and renewable energy. Although the government has issued various policies to catch up, but to realize national energy security, it is necessary to urgently regulate the development of renewable energy as a form of supporting national energy security. As for the formulation of the problems raised in this study are: support national energy security in Indonesia? 2) what is the urgency of regulating the development of renewable energy as a form of supporting national energy security? This research will use normative juridical research and supported by empirical juridical research so that it will be able to see the conditions of developing renewable energy as a form of supporting national energy security in Indonesia. To realize this, it is necessary to urgently regulate the development of renewable energy as a form of supporting national energy security.
ASPIRASI MASYARAKAT DAERAH SEBAGAI PROGRAM PRIORITAS PEMBANGUNAN DAERAH YANG DIJAMIN KONSTITUSI
Authors: Parlindungan S Gokma Toni
Published: July 2021

Aspirations of the people is one key to success for central or regional development. Regional Representative Council as a representative of the people of the region must take the time to listen to the aspirations of local communities. This study will discuss the role of the Regional Legislative Assembly of representatives in the community aspirations as guaranteed by the Constitution. This research method is sociological normative. So this research, is expected to explain the mechanism that is responsive in the aspiration of society by the local council, knowing the role of the Regional Representative Council in voicing the aspirations of the people in the priority programs of regional development. Aspirations of the people is the voice of the people to be delivered in the formation of legislation. So that created regional development priorities is responsive to the community and the region.
POLITIK HUKUM DALAM BIDANG HUKUM KELUARGA ISLAM DI INDONESIA
Authors: Mulyawan Fitra , Yulinda Kiki , Tiara Dora
Published: July 2021

In Indonesia, religion and state are two different entities, and each has its own autonomy, where there is an area that is completely “belonging to” religion, the state cannot enter it and there is also an area that is fully the competence of the state, so religion is not can participate in it. So that the formation of laws will reflect the configuration of power and political interests. In the actualization of political power and interests, sometimes there is a clash between the interests of fragmatism and those that are permanent and in favor of the benefit of mankind. This means that the interests of ideological values that live and develop in society can be configured with the interests of political power fragmatism. Therefore, first, the legislative program for several aspects of the modernization of Islamic family law politics in Indonesia, namely starting with the history of legislation on marriage in Indonesia, one of which is the Dutch East Indies Government circulating the Draft Ordinance on Registered Marriage, which includes the principle of monogamy and the prohibition of imposing divorce out of court. Then from the point of view of the meaning of the ideal law, the presence of KHI is a series of historical national laws that can reveal the various meanings of the life of the Indonesian Muslim community. Second, before the birth of Law no. 1 of 1974 in Indonesia various marriage laws apply for various groups of citizens and various regions. in the Indieche Staats Regeling (ISR), namely the Indian constitutional regulations. After independence, the Indonesian government has established a number of Islamic marriage regulations. Among them are Law Number 22 Year 1946 concerning Registration of Marriage, Divorce and Reconciliation.
HUBUNGAN POLA MAKAN DAN AKTIVITAS FISIK DENGAN PENGENDALIAN KADAR GULA DARAH PADA PENDERITA DIABETES MELITUS TIPE II DI WILAYAH KERJA PUSKESMAS KTK KOTA SOLOK
Authors: Herawati Netty , WD Kurniati Maya Sari
Published: July 2021

Controlling blood sugar levels is the main goal of nursing interventions that will be carried out in Diabetes Mellitus patients. Patients with diabetes mellitus are advised to always have a healthy lifestyle every day. Control blood sugar in DM patients by regulating diet such as: regulating the amount of food, type of food and frequency of eating hours and doing activities (sports). Non-Communicable Diseases (PTM), including Diabetes Mellitus, has now become a serious threat to global health. Quoted from WHO 2016 data, 70% of the world's total deaths and more than half of the disease burden. 90-95% of diabetes cases. Type 2 diabetes, which is largely preventable because it is caused by an unhealthy lifestyle. (Ministry of Health, 2018). Solok City has cases of Diabetes mellitus sufferers in four Puskesmas where there are 284 KTK Puskesmas working areas, while the number of visits to Type II Diabetes mellitus sufferers in the KTK Puskesmas work area is 50 people. Based on the results of research that has been carried out in the Working Area of the KTK Kota Solok Health Center, it was found that more than part (66%) of the respondents 'blood sugar levels were abnormal (high), more than part (64%) of the respondents' diet was not appropriate and more than some (60 %) respondents do not do physical activity regularly. There is a relationship between a diet that is not in accordance with abnormal blood sugar levels and there is a relationship that does not do physical activity with abnormal (high) blood sugar levels in the Working Area of the KTK Kota Solok Health Center. It is hoped that health workers will remind people with Type II Diabetes Mellitus, about the importance of dietary regulation in controlling blood sugar levels and carrying out regular physical activity (exercise) so that it can help in controlling blood sugar levels so that blood sugar levels can be controlled.
FAKTOR-FAKTOR DALAM GLOBALISASI DAN PEMBANGUNAN
Authors: Nurharpani Nurharpani
Published: July 2021

The COVID-19 pandemic has created the need and need to maintain social distance in social interactions (social distancing), quarantine, and isolation so that every vulnerable individual will not be exposed to the virus. The use of technology with online meetings for students and educators is very important, especially in the development of civic education, in order to love the Republic of Indonesia. This paper will discuss the concept and direction of civic education and the urgency of strengthening the concept and direction of progressive citizenship education online in the midst of the covid-19 virus pandemic. The method used in this research is descriptive analytical with a qualitative approach. The results show, First, the concept of Citizenship Education supports the objectives of civic education, which can be interpreted as a subject that focuses on the formation of citizens who have intellectual skills, skills to participate in every civic activity and have a strong civic character so as to make citizens who are intelligent and have character. . Second, the urgency of strengthening the concept and direction of progressive citizenship education online in the midst of the covid-19 virus pandemic prepares students to become good citizens who master knowledge derived from multidisciplinary concepts and theories, practice values, and apply the skills they need to participate. in online education.
ANALISIS PENGARUH INSENTIF TERHADAP PENINGKATAN PRESTASI KERJA KARYAWAN PADA PT. BANK RIAU CABANG PEMBANTU PERAWANG
Authors: Imran Imran
Published: July 2021

Pt. Bank Riau is a continuation of the business activities of PT. BAPERI (PT. Riau Regional Development Bank) which was established based on the Notary Deed of Syawal Sultan No. 1 dated August 2, 1961, and the permission of the Minister of Finance of the Republic of Indonesia.No. BUM 9-4-45 dated August 12, 1961. Furthermore, with the Decree of the Governor of KDH. TK.I Riau No. 51/IV/1966 April 1, 1966, it was stated that all activities of PT. BAPERI was merged into the Riau Regional Development Bank in accordance with Law Number 13 of 1962, officially the activities of the Riau Regional Development Bank began with the status as a Bank Owned by the Government of the Riau Province. Various changes and developments in the Bank's activities, and since 1975 the status of the establishment of the Riau Regional Development Bank, Decree of the Deputy Governor of Bank Indonesia No. 5/30 / KEP.DGS / 2003 dated 22 July 2003, the legal entity status of the Riau Regional Development Bank changed from a Regional Company (PD) Regional Development Bank of Riau to a Limited Liability Company (PT). Bank Pembangunan Daerah Riau was abbreviated as PT. Bank Riau as of August 1, 2003. This research aims to Analyze the Influence of the Incentive Factor on improving the work performance of employees at PT. Bank Riau, Perawang Sub-Branch. The number of research samples are all All employees of PT. Bank Riau, Perawang Sub-Branch, as many as 60 with the sampling method saturated sampling technique or census. Saturated sampling or census is a sampling technique when all members of the population are used as samples.Meanwhile, the leadership is used as the key information in this study. Research result shows The influence of incentives on increasing work performance having a significant influence and positive means that there is a strong positive relationship between incentives and increased work performance of employees of PT. Bank Riau Perawang Sub-Branch, through regression model, the incentive variables and the indicators in the study, are able to contribute to an increase in work performance by 88.36%, and the remaining 11.64% is influenced by other factors who were not examined in this study.

Keywords : Human Resources Management, Incentif, Work Performance.
Oltások az emésztőszervek fertőző betegségeiben: történeti áttekintés
Authors: Buzás György Miklós
Published: July 2021

A járványok évszázadokig megtizedelték az emberiséget, területenként veszélyeztetve egyes népcsoportok fennmaradását. Az oltások története a 18. század végén kezdődött. A bakteriológia és immunológia lehetővé tette az oltóanyagok laboratóriumi fejlesztését: ehhez a baktériumok, és vírusok inaktivációját és attenuálását használták. Ezzel párhuzamosan országonként különböző és időben változó oltási programok alakultak ki. Utóbb kialakultak a sejttenyészetet és virális vektorokat alkalmazó vakcinák. A genetika fejlődésével a 20-21. században lehetőség nyílt molekuláris genetikai markerek segítségével új típusú oltóanyagok bevezetésére, amelyekkel sikeresen lehetett felvenni a harcot számos emésztőszervi fertőző betegséggel (kolera, rotavírus, hepatitis A- és B-vírus-fertőzés). Minden kutatási erőfeszítés ellenére a tudomány adós maradt néhány közegészségügyileg jelentős fertőzésben az oltóanyaggal: ezek a Helicobacter pylori, a hepatitis C-vírus és a Clostridioides difficile-fertőzés.
Bilgi Kaynağı ve Bilgiye Erişim Aracı Olarak İnternet Algısı: Kuşaklararası Yaklaşım Farklılığının Karşılaştırılması
Authors: AKKAYA Mehmet Ali
Published: July 2021

İnternet, son çeyrek yüzyılın insanlık üzerinde en yaygın ve etkili araçlarından biridir. Bilişim teknolojisi alanında günümüzde de devam eden gelişmelerin yanı sıra insanlar üzerindeki etkisine cazibe, kolaylık, hız gibi yetkinlikleri de ekleyen internet, her geçen gün hemen her alanda asıl güçlerden biri olma rolünün çizgilerini daha belirgin hale getirmektedir. Bir yandan birey için dünyayı daha erişilebilir, bildik ve yakından takip edilebilir hale getiren internet, diğer yandan da bu mecra üzerinden dünyaya sunulabilecek ürün ve hizmetler açısından sürekli bir arzın ilhamıdır. Bilgi dünyasını da doğrudan etkileyen internetin algılanması, yorumlanması, değerlendirilmesi ve önemsenmesi noktasında, kuşaklar arasında derin farklılıklar söz konusudur. Öyle ki, günümüzde geldiğimiz noktada söz konusu farklılıkların gözlemlenebilir ayrımlara dönüşmesi için birkaç yıllık yaş farklılıkları dahi belirleyici olabilmektedir. Bu çalışmada; günümüzde toplumda internetin bilgi kaynağı ve/veya bilgiye erişim aracı olarak nasıl değerlendirildiği ve ne düzeyde kıymetli bulunduğunun seçili örneklem grup üzerinden ortaya konulması amaçlanmıştır. Çalışmada elde edilen verilerin daha değerli ve internete yüklenen anlamın seyrinin nasıl olduğunun görülebilmesi için örneklem grubunun ebeveyn ve çocuklarının karşılaştırmasının yapılabileceği ailelerden seçilmesine dikkat edilmiş, böylelikle konuya ilişkin kuşaklararası yaklaşım farklılığının da gösterilmesi hedeflenmiştir. Çalışmada; “internetle daha küçük yaşta tanışan, bu deneyimi artan ve zenginleşen her kuşak, internet-bilgi eşleştirmesini daha çok yapmakta ve bilgiye erişim için interneti çok daha yoğun bir biçimde kullanmaktadır” önermesinden yola çıkılmıştır. Çalışma kapsamında, İzmir’in merkez ilçelerinde yaşayan, biri ilkokul, diğeri ortaokul ve üstü öğrencisi iki çocukları olan aileler ve çocukları ile görüşülerek, her bireyin internetin bilgi kaynağı ya da bilgiye erişim aracı olarak değerlendirilmesi noktasındaki düşüncelerinin/algılarının serimlenmesine çalışılmıştır. Betimleme yöntemi ve anket tekniği ile yürütülen çalışmada elde edilen bulgular, internetin bilgi kaynağı ve/veya bilgiye erişim aracı olarak görülmesi açısından, kuşaklara bağlı algı farklılıklarının olduğunu ortaya koymuştur. Çalışma, ortaya koyduğu veriler üzerinden, ilgili her kuşağın kendi değer yargıları açsından internet-bilgi ilişkisine sorgulayıcı yaklaşımlar geliştirmesine aracılık ettiği ölçüde amacına ulaşmış olacaktır.
Entrainment Dynamics Organised by Global Manifolds in a Circadian Pacemaker Model
Authors: Creaser Jennifer L. , Diekman Casey O. , Wedgwood Kyle C. A.
Published: July 2021

Circadian rhythms are established by the entrainment of our intrinsic body clock to periodic forcing signals provided by the external environment, primarily variation in light intensity across the day/night cycle. Loss of entrainment can cause a multitude of physiological difficulties associated with misalignment of circadian rhythms, including insomnia, excessive daytime sleepiness, gastrointestinal disturbances, and general malaise. This can occur after travel to different time zones, known as jet lag; when changing shift work patterns; or if the period of an individual’s body clock is too far from the 24 h period of environmental cycles. We consider the loss of entrainment and the dynamics of re-entrainment in a two-dimensional variant of the Forger-Jewett-Kronauer model of the human circadian pacemaker forced by a 24 h light/dark cycle. We explore the loss of entrainment by continuing bifurcations of one-to-one entrained orbits under variation of forcing parameters and the intrinsic clock period. We show that the severity of the loss of entrainment is dependent on the type of bifurcation inducing the change of stability of the entrained orbit, which is in turn dependent on the environmental light intensity. We further show that for certain perturbations, the model predicts counter-intuitive rapid re-entrainment if the light intensity is sufficiently high. We explain this phenomenon via computation of invariant manifolds of fixed points of a 24 h stroboscopic map and show how the manifolds organise re-entrainment times following transitions between day and night shift work.
The Influence of Kinematic Constraints on Model Performance During Inverse Kinematics Analysis of the Thoracolumbar Spine
Authors: Alemi Mohammad Mehdi , Burkhart Katelyn A. , Lynch Andrew C. , Allaire Brett T. , Mousavi Seyed Javad , Zhang Chaofei , Bouxsein Mary L. , Anderson Dennis E.
Published: July 2021

Motion analysis is increasingly applied to spine musculoskeletal models using kinematic constraints to estimate individual intervertebral joint movements, which cannot be directly measured from the skin surface markers. Traditionally, kinematic constraints have allowed a single spinal degree of freedom (DOF) in each direction, and there has been little examination of how different kinematic constraints affect evaluations of spine motion. Thus, the objective of this study was to evaluate the performance of different kinematic constraints for inverse kinematics analysis. We collected motion analysis marker data in seven healthy participants (4F, 3M, aged 27–67) during flexion–extension, lateral bending, and axial rotation tasks. Inverse kinematics analyses were performed on subject-specific models with 17 thoracolumbar joints allowing 51 rotational DOF (51DOF) and corresponding models including seven sets of kinematic constraints that limited spine motion from 3 to 9DOF. Outcomes included: (1) root mean square (RMS) error of spine markers (measured vs. model); (2) lag-one autocorrelation coefficients to assess smoothness of angular motions; (3) maximum range of motion (ROM) of intervertebral joints in three directions of motion (FE, LB, AR) to assess whether they are physiologically reasonable; and (4) segmental spine angles in static ROM trials. We found that RMS error of spine markers was higher with constraints than without (p < 0.0001) but did not notably improve kinematic constraints above 6DOF. Compared to segmental angles calculated directly from spine markers, models with kinematic constraints had moderate to good intraclass correlation coefficients (ICCs) for flexion–extension and lateral bending, though weak to moderate ICCs for axial rotation. Adding more DOF to kinematic constraints did not improve performance in matching segmental angles. Kinematic constraints with 4–6DOF produced similar levels of smoothness across all tasks and generally improved smoothness compared to 9DOF or unconstrained (51DOF) models. Our results also revealed that the maximum joint ROMs predicted using 4–6DOF constraints were largely within physiologically acceptable ranges throughout the spine and in all directions of motions. We conclude that a kinematic constraint with 5DOF can produce smooth spine motions with physiologically reasonable joint ROMs and relatively low marker error.
Mining and Biosynthesis of Bioactive Lanthipeptides From Microorganisms
Authors: Li Caiyun , Alam Khorshed , Zhao Yiming , Hao Jinfang , Yang Qing , Zhang Youming , Li Ruijuan , Li Aiying
Published: July 2021

Antimicrobial resistance is one of the most serious public health issues in the worldwide and only a few new antimicrobial drugs have been discovered in recent decades. To overcome the ever-increasing emergence of multidrug-resistant (MDR) pathogens, discovery of new natural products (NPs) against MDR pathogens with new technologies is in great demands. Lanthipeptides which are ribosomally synthesized and post-translationally modified peptides (RiPPs) display high diversity in their chemical structures and mechanisms of action. Genome mining and biosynthetic engineering have also yielded new lanthipeptides, which are a valuable source of drug candidates. In this review we cover the recent advances in the field of microbial derived lanthipeptide discovery and development.
Improving the Production of Riboflavin by Introducing a Mutant Ribulose 5-Phosphate 3-Epimerase Gene in Bacillus subtilis
Authors: Yang Bin , Sun Yiwen , Fu Shouying , Xia Miaomiao , Su Yuan , Liu Chuan , Zhang Chunzhi , Zhang Dawei
Published: July 2021

Ribulose 5-phosphate (Ru5P) and guanosine 5′-triphosphate (GTP) are two key precursors of riboflavin, whereby Ru5P is also a precursor of GTP. Ribulose 5-phosphate 3-epimerase (Rpe) catalyzes the conversion of ribulose 5-phosphate into xylulose 5-phosphate. Inactivation of Rpe can reduce the consumption of Ru5P, enhancing the carbon flux toward riboflavin biosynthesis. Here we investigated the effect of mutation of rpe and other related genes on riboflavin production, physiological and metabolic phenotypes in Bacillus subtilis LY (BSLY). Introducing single nucleotide deletion (generated BSR) or nonsense mutation (generated BSRN) on the genomic copy of rpe, resulting in more than fivefold increase of riboflavin production over the parental strain. BSR process 62% Rpe activity, while BSRN lost the entire Rpe activity and had a growth defect compared with the parent strain. BSR and BSRN exhibited increases of the inosine and guanine titers, in addition, BSRN exhibited an increase of inosine 5′-monophosphate titer in fermentation. The transcription levels of most oxidative pentose phosphate pathway and purine synthesis genes were unchanged in BSR, except for the levels of zwf and ndk, which were higher than in BSLY. The production of riboflavin was increased to 479.90 ± 33.21 mg/L when ribA was overexpressed in BSR. The overexpression of zwf, gntZ, prs, and purF also enhanced the riboflavin production. Finally, overexpression of the rib operon by the pMX45 plasmid and mutant gnd by pHP03 plasmid in BSR led to a 3.05-fold increase of the riboflavin production (977.29 ± 63.44 mg/L), showing the potential for further engineering of this strain.
A Timed Off-Switch for Dynamic Control of Gene Expression in Corynebacterium Glutamicum
Authors: Siebert Daniel , Altenbuchner Josef , Blombach Bastian
Published: July 2021

Dynamic control of gene expression mainly relies on inducible systems, which require supplementation of (costly) inducer molecules. In contrast, synthetic regulatory circuits, which allow the timed shutdown of gene expression, are rarely available and therefore represent highly attractive tools for metabolic engineering. To achieve this, we utilized the VanR/PvanABK* regulatory system of Corynebacterium glutamicum, which consists of the transcriptional repressor VanR and a modified promoter of the vanABK operon (PvanABK*). VanR activity is modulated by one of the phenolic compounds ferulic acid, vanillin or vanillic acid, which are co-metabolized with d-glucose. Thus, gene expression in the presence of d-glucose is turned off if one of the effector molecules is depleted from the medium. To dynamically control the expression of the aceE gene, encoding the E1 subunit of the pyruvate dehydrogenase complex that is essential for growth on d-glucose, we replaced the native promoter by vanR/PvanABK* yielding C. glutamicum ΔPaceE::vanR-PvanABK*. The biomass yield of this strain increased linearly with the supplemented amount of effector. After consumption of the phenolic compounds growth ceased, however, C. glutamicumΔPaceE::vanR-PvanABK* continued to utilize the residual d-glucose to produce significant amounts of pyruvate, l-alanine, and l-valine. Interestingly, equimolar concentrations of the three phenolic compounds resulted in different biomass yields; and with increasing effector concentration, the product spectrum shifted from pyruvate over l-alanine to l-valine. To further test the suitability of the VanR/PvanABK* system, we overexpressed the l-valine biosynthesis genes ilvBNCE in C. glutamicum ΔPaceE::vanR-PvanABK*, which resulted in efficient l-valine production with a yield of about 0.36 mol l-valine per mol d-glucose. These results demonstrate that the VanR/PvanABK* system is a valuable tool to control gene expression in C. glutamicum in a timed manner by the cheap and abundant phenolic compounds ferulic acid, vanillin, and vanillic acid.
Chemical Synthesis of the Sec-To-Cys Homologue of Human Selenoprotein F and Elucidation of Its Disulfide-pairing Mode
Authors: Liao Peisi , He Chunmao
Published: July 2021

Herein, we document a highly optimized synthesis of the Sec-to-Cys homologue of the human selenoprotein F (SelF) through a three-segment two-ligation semisynthesis strategy. Highlighted in this synthetic route are two one-pot manipulations, i.e. the first ligation followed by a desulfurization and the second ligation followed by the protein refolding. This way multi-milligrams of the folded synthetic protein was obtained, which set the stage for the synthesis of the natural selenoprotein. Moreover, the disulfide pairing mode of the SelF was elucidated through a combination of site-directed mutagenesis and LC-MS study. It provides not only a criterion to judge the viability of the synthetic protein, and more importantly, useful structural insights into the previously unresolved UGGT-binding domain of SelF.
Enzyme-Loaded pH-Sensitive Photothermal Hydrogels for Mild-temperature-mediated Combinational Cancer Therapy
Authors: Xia Jindong , Qing Xueqin , Shen Junjian , Ding Mengbin , Wang Yue , Yu Ningyue , Li Jingchao , Wang Xiuhui
Published: July 2021

Photothermal therapy (PTT) that utilizes hyperthermia to ablate cancer cells is a promising approach for cancer therapy, while the generated high temperature may lead to damage of surrounding normal tissues and inflammation. We herein report the construction of glucose oxidase (GOx)-loaded hydrogels with a pH-sensitive photothermal conversion property for combinational cancer therapy at mild-temperature. The hydrogels (defined as CAG) were formed via coordination of alginate solution containing pH-sensitive charge-transfer nanoparticles (CTNs) as the second near-infrared (NIR-II) photothermal agents and GOx. In the tumor sites, GOx was gradually released from CAG to consume glucose for tumor starvation and aggravate acidity in tumor microenvironment that could turn on the NIR-II photothermal conversion property of CTNs. Meanwhile, the released GOx could suppress the expression of heat shock proteins to enable mild NIR-II PTT under 1,064 nm laser irradiation. As such, CAG mediated a combinational action of mild NIR-II PTT and starvation therapy, not only greatly inhibiting the growth of subcutaneously implanted tumors in a breast cancer murine model, but also completely preventing lung metastasis. This study thus provides an enzyme loaded hydrogel platform with a pH-sensitive photothermal effect for mild-temperature-mediated combinational cancer therapy.
Tissue/Biofluid Specific Molecular Cartography of Leishmania donovani Infected BALB/c Mice: Deciphering Systemic Reprogramming
Authors: Das Sanchita , Saha Tanaya , Shaha Chandrima
Published: July 2021

Pathophysiology of visceral leishmaniasis (VL) is not fully understood and it has been widely accepted that the parasitic components and host immune response both contribute to the perpetuation of the disease. Host alterations during leishmaniasis is a feebly touched area that needs to be explored more to better understand the VL prognosis and diagnosis, which are vital to reduce mortality and post-infection sequelae. To address this, we performed untargeted metabolomics ofLeishmania donovani(Ld) infected, uninfected and treated BALB/c mice’s tissues and biofluids to elucidate the host metabolome changes using gas chromatography–mass spectrometry. Univariate and multivariate data treatments provided numerous significant differential hits in several tissues like the brain, liver, spleen and bone marrow. Differential modulations were also observed in serum, urine and fecal samples of Ld-infected mice, which could be further targeted for biomarker and diagnostic validations. Several metabolic pathways were found to be upregulated/downregulated in infected (TCA, glycolysis, fatty acids, purine and pyrimidine, etcetera) and treated (arginine, fumaric acid, orotic acid, choline succinate, etcetera) samples. Results also illustrated several metabolites with different pattern of modulations in control, infected and treated samples as well as in different tissues/biofluids; for e.g. glutamic acid identified in the serum samples of infected mice. Identified metabolites include a range of amino acids, saccharides, energy-related molecules, etcetera. Furthermore, potential biomarkers have been identified in various tissues—arginine and fumaric acid in brain, choline in liver, 9-(10) EpOME in spleen and bone marrow, N-acetyl putrescine in bone marrow, etcetera. Among biofluids, glutamic acid in serum, hydrazine and deoxyribose in urine and 3-Methyl-2-oxo pentanoic acid in feces are some of the potential biomarkers identified. These metabolites could be further looked into for their role in disease complexity or as a prognostic marker. The presented profiling approach allowed us to attain a metabolic portrait of the individual tissue/biofluid modulations during VL in the host and represent a valuable system readout for further studies. Our outcomes provide an improved understanding of perturbations of the host metabolome interface during VL, including identification of many possible potential diagnostic and therapeutic targets.
Coatings in Decellularized Vascular Scaffolds for the Establishment of a Functional Endothelium: A Scoping Review of Vascular Graft Refinement
Authors: Heng Jun Wei , Yazid Muhammad Dain , Abdul Rahman Mohd Ramzisham , Sulaiman Nadiah
Published: July 2021

Developments in tissue engineering techniques have allowed for the creation of biocompatible, non-immunogenic alternative vascular grafts through the decellularization of existing tissues. With an ever-growing number of patients requiring life-saving vascular bypass grafting surgeries, the production of functional small diameter decellularized vascular scaffolds has never been more important. However, current implementations of small diameter decellularized vascular grafts face numerous clinical challenges attributed to premature graft failure as a consequence of common failure mechanisms such as acute thrombogenesis and intimal hyperplasia resulting from insufficient endothelial coverage on the graft lumen. This review summarizes some of the surface modifying coating agents currently used to improve the re-endothelialization efficiency and endothelial cell persistence in decellularized vascular scaffolds that could be applied in producing a better patency small diameter vascular graft. A comprehensive search yielding 192 publications was conducted in the PubMed, Scopus, Web of Science, and Ovid electronic databases. Careful screening and removal of unrelated publications and duplicate entries resulted in a total of 16 publications, which were discussed in this review. Selected publications demonstrate that the utilization of surface coating agents can induce endothelial cell adhesion, migration, and proliferation therefore leads to increased re-endothelialization efficiency. Unfortunately, the large variance in methodologies complicates comparison of coating effects between studies. Thus far, coating decellularized tissue gave encouraging results. These developments in re-endothelialization could be incorporated in the fabrication of functional, off-the-shelf alternative small diameter vascular scaffolds.
Reconstructing the Climate Variability During the Last 5000 Years From the Banni Plains, Kachchh, Western India
Authors: Makwana Nisarg , Prizomwala S. P. , Das Archana , Phartiyal Binita , Sodhi Aashima , Vedpathak Chintan
Published: July 2021

The climatic conditions during the beginning of the last 5,000 years have been discussed, debated, and documented from various parts of the Indian subcontinent, due to the human–climate interrelationship. In the present study, we report a multi-proxy dataset encompassing the widely used ∼ geochemical and mineral magnetic proxies supported by radiocarbon and optical chronologies from the Banni Plains of the Rann of Kachchh, western India. Our results support the earlier observations of the prolonged wetter climatic condition synchronous with the mature phase of Harappan era which witnessed a short and intense arid condition at the terminal part of the mature Harappan phase. The climate system dramatically fluctuated during the last five millennia from pulsating between relatively arid (4,800–4,400 years BP, 3,300–3,000 years BP, and at 2,400 years BP) and relatively humid phases (>4,800 years BP, 4,000–3,300 years BP, 1900–1,400 years BP, and 900–550 years BP). The multi-proxy dataset shows a gradual strengthening of the monsoonal conditions from the Banni Plains during the late Harappan phase. Apart from this, the high sedimentation rate (>1 mm/yr) recorded from the Banni Plains suggests it can be tapped as a robust archive to reconstruct multi-decadal to centennial climatic events spanning the Holocene epoch.
Impact of Sodium Butyrate Treatment in LPS-Stimulated Peripheral Blood Mononuclear Cells of Poorly Controlled Type 2 DM
Authors: Wibowo Heri , Harbuwono Dante S. , Tahapary Dicky L. , Kartika Rona , Pradipta Saraswati , Larasati Rahma A.
Published: July 2021

Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammation, which is marked by the dysregulation of innate and adaptive immune responses. Therefore, reducing inflammation, possibly through an immunoregulatory agent, may play a role in T2DM treatment. Butyrate is the most potent short-chain fatty acid (SCFA), and it exerts anti-inflammatory properties by inhibiting histone deacetylase activity. As an immunoregulatory agent, sodium butyrate can inhibit nuclear factor kB (NF-kB) activation and reduce the production of pro-inflammatory cytokines in immune cells. The aim of the study was to measure the level of plasma butyrate in poorly controlled T2DM and normoglycemic participants and to compare the response of peripheral blood mononuclear cells (PBMCs) to sodium butyrate treatment between the groups by measuring production of the following cytokines: tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-13, and IL-10. The in vitro study examined the PBMCs of 15 participants with poorly controlled T2DM and 15 normoglycemic participants. PBMCs were cultured with the following stimulations for two days at a temperature of 37°C and 5% CO2: 100 ng/mL lipopolysaccharide (LPS), 1 mM sodium butyrate, or a combination of 100 ng/mL LPS and 1 mM sodium butyrate. Plasma butyrate was measured using gas chromatography-mass spectrometry, and cytokines from culture supernatant were analyzed using magnetic beads multiplex assay. Plasma butyrate levels in participants with poorly controlled T2DM did not significantly differ from those in normoglycemic participants (p = 0.105). Compared to treatment with an LPS-stimulated PBMC culture, treatment with 1 mM sodium butyrate reduced the levels of TNF-α (p < 0.039) and IFN-γ (p < 0.038) in normoglycemic participants. The same general trend was seen in PBMC from participants with poorly controlled T2DM, but higher variability appeared to preclude statistical significance. These data suggest that butyrate may modulate inflammatory cytokine production in human PBMCs, but more research is needed to determine if butyrate is anti-inflammatory in poorly controlled T2DM.
Body Composition and Serum Anti-Müllerian Hormone Levels in Euthyroid Caucasian Women With Hashimoto Thyroiditis
Authors: Adamska Agnieszka , Popławska-Kita Anna , Siewko Katarzyna , Łebkowska Agnieszka , Krentowska Anna , Buczyńska Angelika , Popławski Łukasz , Szumowski Piotr , Szelachowska Małgorzata , Krętowski Adam Jacek , Kowalska Irina
Published: July 2021

Objective

Women with Hashimoto thyroiditis (HT) are characterized by increased incidence of infertility and disturbances in body composition. Serum anti-Müllerian hormone (AMH), which reflects functional ovarian reserve, is decreased in women with HT and it be related to body mass. The aim of the present study was to investigate the relation between serum levels of AMH and body composition in HT compared to control group.

Patients and Methods

We examined 85 euthyroid women: 39 subjects with HT and 46 control women. Body composition was analysed by dual-energy X-ray absorptiometry and with bioimpedance method. Serum concentrations of AMH, leptin, TSH, thyroid hormones were assessed.

Results

We observed lower serum concentration of AMH in women with HT in comparison to the control group (p=0.01), but without differences in serum concentration of leptin between studied groups (p=0.28). Women with HT were characterized by higher %body fat (p=0.01) estimated with bioimpedance method without differences in BMI, android and gynoid fat mass and visceral adipose tissue (VAT) mass estimated with DXA method when compared to the control group (all p>0.05). We found a negative relationship between serum concentration of AMH and %body fat (r=-0.38,p=0.03) in women with HT. Additionally, in HT group, the relationship between serum levels of AMH and leptin was not statistically significant (r=0.01,p=0.96). We observed a relationship between serum concentration of leptin and BMI, %body fat mass, android, gynoid and VAT mass in HT and in the control group (all p<0.01).

Conclusions

Women with HT are characterized by lower levels of AMH and it is associated with higher fat mass, independently of serum levels of leptin.