Preliminary Activities Research Articles

Phase I/II combination study of tifcemalimab with toripalimab in patients with refractory extensive stage small cell lung cancer (ES-SCLC).

8579 Background: The B- and T-lymphocyte attenuator (BTLA) is a novel inhibitory co-signaling receptor expressed on B cell, T cells and NK cells. Co-blockade of the BTLA and PD-1 pathways improved antigen specific anti-tumor T cell response. Tifcemalimab (JS004 or TAB004) is a humanized IgG4 monoclonal antibody with a hinge mutation (S228P) that binds BTLA and blocks its interaction with its ligand HVEM. In previous phase I studies, tifcemalimab has shown preliminary anti-tumor activities as monotherapy or in combination with toripalimab (anti-PD-1) with a manageable safety profile in patients with advanced malignancies. Methods: Eligible ES-SCLC patients refractory to prior therapies were enrolled in this I/II study (NCT05000684). Patients received 200mg tifcemalimab and 240mg toripalimab intravenously once every three weeks until disease progression, intolerable toxicity or 2 years of treatment. Study objectives included safety, anti-tumor activity and correlative biomarkers. Results: As of Jan 31, 2023, a total of 43 ES-SCLC patients refractory to prior therapy were enrolled. The median age was 60.0 (range 38-75) years. The median prior line of therapy was 1 and 14 (32.6%) patients received prior anti-PD-1/L1 treatment. By the cut-off date, the median follow-up duration was 12.1 weeks. Thirty-two (74.4%) patients experienced treatment-emergent adverse events (TEAEs); 12 (27.9%) patients experienced grade ≥ 3 TEAEs. The most common TEAEs were hyponatraemia (16.3%), alanine aminotransferase increased (14%), aspartate aminotransferase increased (14%), and blood creatine phosphokinase increased (14%). Three (7.0%) patients experienced treatment-related adverse events (TRAEs) led to interruption of study drugs and no TRAEs led to discontinuation of study drugs were reported. Fifteen (34.9%) patients experienced immune related AE (irAEs), and 2 (4.7%) patients experienced grade ≥ 3 irAEs. Among 38 efficacy evaluable patients, the ORR was 26.3% and the DCR was 57.9%. The ORR was 8.3% in immunotherapy treated patients and 40.0% in immunotherapy naïve patients. By the cut-off date, 70.0% of the responses were ongoing and the median duration of response was not reached. Tumor expression of HVEM and PD-L1 was evaluated to explore the correlation with clinical response. Conclusions: Tifcemalimab in combination with toripalimab were well tolerated in patients with refractory ES- SCLC. Further clinical evaluation of this combination treatment in SCLC is warranted. Clinical trial information: NCT05000684 .

Preliminary results of a phase 1/2, first-in-human, open-label, dose escalation study of ZL-1211 (anti-Claudin 18.2 mAb) in patients with unresectable or metastatic solid tumors.

2537 Background: ZL-1121 is a humanized immunoglobulin G1 monoclonal antibody targeting Claudin18.2. Site mutations (S239D and I332E) were introduced in the Fc portion of ZL-1211 to enhance antibody dependent cellular cytotoxicity. Herein, we present the preliminary results from the ongoing dose escalation part of the study. Methods: This is a first-in-human, phase 1/2, multicenter, dose escalation/cohort expansion study of ZL-1211 administered intravenously to adult patients with Claudin 18.2-positive advanced solid tumors. A Bayesian optimal interval design with 3+3 run-in was adopted to assess 5 dose levels of ZL-1211 monotherapy (1 to 40 mg/kg biweekly) for phase 1 dose escalation, followed by phase 2 cohort expansion. The primary objectives were to determine the maximum tolerated dose and/or the recommended phase 2 dose, assess the safety/tolerability, and evaluate the preliminary antitumor activities of ZL-1211. Tumor assessments were performed every 8 weeks per RECIST v1.1. Blood samples were collected for pharmacokinetic (PK) analyses. Results: As of Dec 12, 2022, 19 patients (11 pancreatic cancer, 6 gastric cancer, 1 esophageal cancer, and 1 bile duct cancer) had been enrolled in the dose escalation phase to receive ZL-1211 at 1 mg/kg (n = 3), 5 mg/kg (n = 7), 10 mg/kg (n = 4), and 20 mg/kg (n = 5). The median age was 60 years and the majority of the patients (78.9%) received ≥2 lines of prior systemic therapy. No dose limiting toxicities (DLT) had been observed as of the cut-off date. The most common treatment-related adverse events (TRAEs) were gastrointestinal disorders, including nausea (11/19, 57.9%), vomiting (6/19, 31.6%), and abdominal pain (3/19, 15.8%). Other common TRAEs (≥15%) were hypoalbuminaemia (3/19, 15.8%) and infusion-related reactions (3/19, 15.8%). Grade 3 TRAEs occurred in 3 patients, 1 with nausea and vomiting, 1 with platelet count decreased, and 1 with anaemia, leukopenia, platelet count decreased, and weight decreased. No Grade ≥ 4 TRAEs were reported. Two patients experienced serious TRAEs: 1 reporting 2 cases each of grade 3 vomiting and nausea and 1 reporting a grade 3 platelet count decreased and a grade 2 abdominal pain, all of which had recovered. TRAEs led to treatment interruption in 5 patients (26.3%) and treatment withdrawal in 1 patient (5.3%). No TRAEs leading to death were reported. Six of 9 tumor-evaluable patients achieved stable disease as the best overall response. Three patients had tumor regression: 17.1% in a pancreatic cancer patient of the 5 mg/kg cohort; 14.5% in a pancreatic cancer patient and 24.9% in a gastric cancer patient in the 10 mg/kg cohort. Preliminary PK analyses revealed linear PK of ZL-1211 over the dose range tested. Conclusions: ZL-1211 displayed an acceptable safety/tolerability profile to date and demonstrated preliminary antitumor effects. Clinical trial information: NCT05065710 .

Implementation of Local Content Learning from the Book of Mabadi' Al-Fiqhiyyah at Madrasah Ibtidaiyah Ma'arif

The study of fiqh is considered very important in order to discover what Allah SWT forbids and recommends, and it has various concrete implications for individual and community daily actors. Madrasah Ibtidaiyah Ma'arif Pagerwojo are schools that teach mabadi'ul fiqhiyyah as a local content that is not taught at other madrasas. Therefore this study aims to discover the goals, topics and steps involved in learning the local content of the Mabadi'ul Fiqhiyyah and its assessment instruments. Descriptive qualitative methods were used in this study, with data gathered through interviews, observations, and documentation. This research data was analyzed using Miles and Huberman's data analysis techniques. According to the findings of this study, the goal of learning the book of Mabadi'ul Fiqhiyyah is to introduce Islamic values and principles of fiqhiyyah using Arabic. And this book contains fiqh principles as well as an understanding of basic fiqh laws such as prayer, ablution, and those related to them. The teaching method, aided by audio-visual media, is then used for the learning steps with preliminary activities and core activities. Written tests, oral tests, and practical exams are used to assess learning and are held twice a year.

PEMBELAJARAN INTEGRATIF MATA PELAJARAN SEJARAH KEBUDAYAAN ISLAM DALAM MEMBENTUK KARAKTER CINTA DAMAI DAN TANAH AIR SISWA KELAS IX MADRASAH TSANAWIYAH TARBIYATUL MUBTADIIN WILALUNG GAJAH DEMAK

Integrative learning and peace-loving character building is something that needs to be studied and researched because character is a very interesting issue to develop, thus, this study aims to analyze the design, and implementation of SKI integrative learning in building character. The research method used is qualitative and naturalistic through participant observation. Data collection techniques using observation, interviews, and documentation. The results of this study indicate: 1) Integrative learning design is structured to include strengthening character education, literacy, higher order thinking skills, and 4C (critical thinking, collaboration, communication, and creativity), 2) Integrative learning includes preliminary activities, core activities and activities closing. In integrative learning using the integration of brainstorming methods with discussions, Numbered heads together (NHT) with cooperative scripts; 3) Assessment of integrative learning outcomes includes three domains which include aspects of attitudes, aspects of knowledge, and aspects of skills. The implication of the results of this study is that integrative learning with the formation of student character can be carried out well if it is supported by all components and factors that exist in the educational circulation itself. If integrative learning is successful, then character education is also successful, and vice versa.

PEMBELAJARAN JOYFULL LEARNING DENGAN PUZZLE GAME BERBASIS EKSPERIMEN: MENINGKATKAN MINAT BELAJAR SISWA MATA PELAJARAN IPA

This study aims to describe the implementation of Joyful Leaning learning with Experiment-based Puzzle Games in increasing student learning interest in Class IV Science at MI Muhammadiyah 2 Kudus accompanied by various factors that support and hinder it. This research is included in the descriptive qualitative research where the type of research is field research. Data will be obtained through interviews, observation and documentation of research subjects, namely teachers and students at MI Muhammadiyah 2 Kudus. The validity of the data obtained will be tested by testing the validity of the data in the form of extending observations, increasing persistence and member checks. The data analysis that will be carried out uses Miles and Huberman's theory. The results of this study indicate that the application of Experiment-based Joyful Learning with Puzzle Games in class IV Science subjects at MI Muhammadiyah 2 Kudus begins with preliminary activities, core activities and closing activities. Joyful Learning Learning with Experiment-based Puzzle Game was able to increase students' interest in learning, namely at the 1st meeting with results (55%: Fairly Good), 2nd meeting with results (60%: Fairly Good), 3rd meeting with results ( 64% : Good), and the 4th meeting with results (66% : Good). The supporting factors for Joyful Learning with experimental-based Puzzle Games are teachers and students, while the inhibiting factors are facilities and infrastructure as well as observational tools and materials. Factors supporting interest in learning for grade IV students in Science Subjects, namely teachers, students, student conditions, class conditions and the inhibiting factors are the lack of parental assistance and appreciation given by outstanding students as well as item numbers 9 and 14 indicators of interest in learning.

Penerapan Metode Time Line Dalam Pembelajaran PAI di SMA N 1 Tanjung Mutiara

The background of this research is that some students have a low level of awareness in participating in PAI learning activities, especially about historical material. Students are less enthusiastic in participating in learning and students are less involved in the process of teaching and learning activities. From the problems that exist, researchers are interested in examining the application of the time line method in PAI learning at SMAN 1 Tanjung Mutiara and its inhibiting factors. This study aims to find out how the application of the Time line learning method and its inhibiting factors. This type of research is descriptive qualitative research which describes the application of the time line method in PAI learning at SMAN 1 Tanjung Mutiara. In collecting data researchers used observation techniques, interviews and documentation. Meanwhile, to analyze it, the researcher uses data reduction, data presentation and conclusion drawing. Researchers checked the data that had been obtained from various research instruments, namely teachers, principals and students using source triangulation, researcher triangulation and method triangulation. So as to produce a credible conclusion. From the research that has been done, it can be concluded that the application of the time line method in PAI learning at SMAN 1 Tanjung Mutiara starts with teacher planning in preparing lessons by making lesson plans which serve as teacher guidelines in teaching and learning activities carried out in the classroom. The application of the Time Line method in learning is carried out through three activities, namely preliminary activities, core activities and closing activities. The essence of applying the time line method is that students observe, analyze and discover for themselves related to learning in discussion activities. The inhibiting factors found were the short time allocation, the teacher's ability to link learning, students playing around during discussions, and female students being more active than male students.

Implementasi Model PAIKEM GEMBROT dalam Pembelajaran PAIBP pada Kelas II dan V di SDN 06 Batang Anai Kabupaten Padang Pariaman

This study aims to determine the planning, implementation, and evaluation of the GEMBROT PAIKEM model in PAIBP learning in class II and class V. This research is a qualitative descriptive research method with a case study type of method. Informants in this study were PAIBP teachers and school principals with data collection techniques namely observation, interviews, and documentation, while data analysis techniques used data collection, data reduction, data presentation, and drawing conclusions and verification. Based on the research results, it was found that the implementation of the PAIKEM GEMBROT model in PAIBP learning in grades II and V was divided into three stages, namely preliminary activities, core activities, and closing activities. Planning for the PAIKEM GEMBROT model in PAIBP learning in grades II and V is carried out by determining the next material which is guided by the syllabus, PROTA, PROMES, daily journals, then determining learning objectives, KD, achievement indicators, so that it becomes a lesson plan. Evaluation of the GEMBROT PAIKEM model in PAIBP learning in grades II and V is divided into three assessments, namely knowledge (cognitive), attitude (affective), and skills (psychomotor).

Abstract 1880: A novel CD137 agonist exhibits potent antitumor efficacy with a good safety profile

Abstract Background: CD137 (TNFRSF9, 4-1BB) is a member of the tumor necrosis factor receptor superfamily that functions as a costimulatory molecule of immunocytes and is mainly expressed on the surface of immune cells including activated T and natural killer (NK) cells. Agonists against CD137 have shown promising therapeutic activity in mouse tumor models but have suffered setback in the clinic due to notably hepatotoxicity, or suboptimal agonistic potency. Here, we developed a fully human agonistic anti-CD137 monoclonal IgG4 antibody, ZG033, with an exclusive epitope, to achieve a better efficacy and safety profile for immunotherapy. Methods: The antigen binding specificity and affinity of ZG033 were determined by ELISA, surface plasmon resonance (SPR). X-ray crystallography was conducted to resolve the binding epitopes of the respective binding arms. The activities were determined using cell-based and reporter gene assays. In vivo antitumor activities were evaluated in human 4-1BB transgenic mice bearing with syngeneic tumors, and possible toxicity was evaluated in humanized mice and cynomolgus monkeys. Cytokine release assay was conducted by incubating ZG033 with PBMCs from healthy donors. The pharmacokinetic (PK) behavior of ZG033 were characterized in cynomolgus monkeys. A phase 1 study was initiated to evaluate the safety and preliminary clinical activities of ZG033, as well as the immunogenicity and pharmacokinetics. Results: ZG033 showed high specificity for human CD137 without cross-species reactivity across mouse, rat and exhibited potent CD137 agonist activity dependent on FcγR crosslinking. The binding affinity of ZG033 determined by surface plasmon resonance (SPR) was moderate (KD=10 nM). X-ray crystallography revealed that the Fab of ZG033 binds CD137 at an epitope overlap with the ligand binding interface. ZG033 increased CD137-driven NFκB reporter gene activation and the production of IFN-γ by human T cells in a FcγR-dependent manner. In human CD137 transgenic mice, ZG033 showed robust antitumor activity and induced durable antigen-specific immunological memory that prevented the tumor formation in the rechallenged mice. There were no signs of toxicity in human cytokine release assay which confirmed that ZG033 did not induce pro-inflammatory cytokines in the absence of TCR stimulation. Toxicology data in mice showed that ZG033 was well-tolerated with normal ALT and AST levels. ZG033 was further confirmed to well tolerated up to 180 mg/kg (MTD≥180mg/kg) dose without systemic toxicity in cynomolgus monkeys. Patients with advanced tumors, who are refractory after exhausting available therapies, were enrolled for ZG033 treatment. We will report the results from early dose escalation part of the study. Conclusion: These data demonstrate that ZG033 is an FcγR crosslinking-dependent CD137 agonist that displays a favorable safety profile and has potential in either mono- or combinational immunotherapies. Citation Format: Yang Huang, Liangwei Li, Wenting Liu, Dayan Zhang, Pengfei Zhou, Qing Fang, Weiming Zhou, Fengrong Wang, Guodong Shen, Liansheng Cheng. A novel CD137 agonist exhibits potent antitumor efficacy with a good safety profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1880.

EVALUASI PELAKSANAAN PEMBELAJARAN BAHASA ARAB BERBASIS KURIKULUM 2013 KELAS V SD AL-AMIN CEMANI GROGOL SUKOHARJO

Learning Implementation Plan is an important component of learning. However, in practice, it is known that teachers at Al-Amin Elementary School still consider lesson plans to be only administrative completeness requirements and teachers still miss some of the implementation components in the implementation components of lesson plans. This study aims to evaluate the implementation of the Arabic language learning process at SD Al-Amin Cemani Grogol Sukoharjo. This research is a qualitative descriptive study. The research subject is an Arabic teacher. Data collection using the method of observation, interviews and document study. Then data analysis using data reduction, data presentation and data verification. The research data was checked for the validity of the data using the triangulation technique. The results of this study indicate that in the process of implementing Arabic language learning using the 2013 curriculum which was carried out by the Arabic teacher at Al-Amin Cemani Grogol Sukoharjo Elementary School, the implementation of learning starting from preliminary activities, core activities and closing activities has been carried out, but the implementation of learning is written in RPP is not all implemented by the teacher during the learning process in the field. The teacher also has several obstacles in the implementation of learning, however the teacher has a strategy to overcome these obstacles.

IMPLEMENTASI PEMBELAJARAN PENDIDIKAN AGAMA HINDU DAN BUDI PEKERTI PADA MASA PANDEMI COVID-19 DI SMP PGRI 2 DENPASAR

The COVID-19 pandemic has affected the education system in Indonesia, according to the SE of the Ministry of Education and Culture Number 4 of 2020 concerning the Implementation of Education in the Coronavirus Disease (Covid-19) Emergency Period. In this condition, all teachers or educators are required to replace learning using E-learning or through online media, including at SMP PGRI 2 Denpasar. The formulation of the problems that will be studied in this research are: (1) How is the planning of learning Hindu religion and manners during the Covid-19 pandemic at SMP PGRI 2 Denpasar?, (2) How is the implementation of learning Hindu religion and manners during the Covid pandemic? -19 at SMP PGRI 2 Denpasar?, (3) How is the evaluation of learning Hindu religion and manners during the Covid-19 pandemic at SMP PGRI 2 Denpasar?. This study aims to: (1) describe the planning of learning Hindu religion and manners during the Covid-19 pandemic, (2) Analyzing the implementation of Hindu religious learning and manners during the Covid-19 pandemic, (3) Analyzing how to evaluate Hindu religious learning and manners during the Covid-19 pandemic at SMP PGRI 2 Denpasar, the problems in this study were studied using constructivism theory and behaviorism theory. This study uses data collection techniques of observation, interviews, literature study, documentation. The data that has been collected was analyzed using qualitative descriptive analysis techniques through three stages of data reduction activities, data presentation, and conclusion drawing. Based on the results of research and data analysis, it shows that: (1) planning for learning Hinduism and manners during the Covid-19 pandemic at SMP PGRI 2 Denpasar through the stages of preparing the design of learning materials, preparing learning media and choosing Hindu religion and character learning methods in the time of the covid-19 pandemic. (2) the implementation of learning about Hindu religion and manners during the Covid-19 pandemic at SMP PGRI 2 Denpasar through preliminary activities, core activities, and closing activities. (3) evaluation of learning Hindu religion and manners during the Covid-19 pandemic at SMP PGRI 2 Denpasar through assessment of student knowledge, assessment of student attitudes and assessment of student skills.
 Keywords: Learning, Hindu religious education and manners, the Covid-19 pandemic

Complexes of 2-Amino-3-methylpyridine and 2-Amino-4-methylbenzothiazole with Ag(I) and Cu(II): Structure and Biological Applications

Coordination complexes (1–4) of 2-amino-4-methylbenzothiazole and 2-amino-3-methylpyridine with Cu(CH3COO)2 and AgNO3 were prepared and characterized by UV/Vis and FT-IR spectroscopy. The molecular structure for single crystals of silver complexes (2 and 4) were determined by X-ray diffraction. The coordination complex (2) is monoclinic with space group P21/c, wherein two ligands are coordinated to a metal ion, affording distorted trigonal geometry around the central Ag metal ion. The efficient nucleophilic center, i.e., the endocyclic nitrogen of the organic ligand, binds to the silver metal. Ligands are coordinated to adopt cis arrangement, predominantly due to steric reasons. The O(2) and O(3) atoms of the NO3− group further play an important role in such type of ligand arrangement by hydrogen bonding with the NH2 group of ligands. Complex (4) is orthorhombic, P212121, comprising two molecules of 2-amino-3-methylpyridine as ligand coordinated with the metal ion, affording a polymeric structure. The coordination behavior of the ligand is identical to that in complex 2, wherein ring nitrogen is coordinated to the metal center and bridged to another metal ion through an NH2 group. The resulting product is polymeric in nature with the Ag metal in the backbone and ligand as the bridge. Compounds (2–4) were found to be luminescent, while 1 did not show such activity. All compounds were screened for their preliminary biological activities such as antibacterial, antioxidant and enzyme inhibition. Compounds exhibited moderate activity in these tests.

Analisis Kemampuan PCK Calon Guru Melalui Pembuatan PaP-eRs

A study involving final year students who are carrying out PPL. The purpose of this study was to analyze the Pedagogical Content Knowledge (PCK) ability of prospective teachers in reflecting on learning after carrying out learning practices. The study is focused on making Pedagogical and Professional Repertoires (PaP-eRs). PaP-eRs are narratives of learning activities created by prospective teachers. The making of the narrative is intended so that prospective teachers can reflect on their learning. The research subjects were six prospective teachers who were carrying out PPL in schools that had been determined by the study program. The instrument used as a data collection tool in this study was the PaP-eRs. The collected PaP-eRs were then analyzed using the PaP-eRs analysis format. The results of the PaP-eRs analysis show that the narrated learning activities include preliminary activities, core activities and closing activities. However, each activity is only narrated in outline so that the narrative cannot be used as a reflection of learning. This shows that the ability of PCK prospective teachers to reflect on learning through creating learning narratives (PaP-eRs) is still low

First-in-human, phase I study of AK109, an anti-VEGFR2 antibody in patients with advanced or metastatic solid tumors

Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in antiangiogenesis which has been an essential strategy for cancer treatment. We report the first-in-human study of AK109, a novel anti-VEGFR2 monoclonal antibody, to characterize the safety profile and pharmacokinetics/pharmacodynamics (PK/PD) properties, and explore the preliminary antitumor efficacy in patients with solid tumors. This was a multicenter, open-label, phase I study, including dose escalation and dose expansion (NCT04547205). Patients with advanced cancers were treated 2 and 3 weekly with escalating doses of AK109. A 3+ 3 design was used to determine the maximum tolerated dose. Blood was sampled for PK/PD analysis. The primary endpoint was safety and recommended phase II dose (RP2D). A total of 40 patients were enrolled. No dose-limiting toxicity was observed. However, 38 patients reported treatment-related adverse events (TRAEs); grade ≥3 TRAEs occurred in 10 patients. The most common TRAEs were proteinuria (n= 24, 60%), hypertension (n= 13, 32.5%), increased aspartate transaminase (n= 11, 27.5%), thrombopenia (n= 10, 25%), and anemia (n= 10, 25%). A total of 28 patients (70%) reported adverse events of special interest (AESIs). The most common AESIs were proteinuria (60%), hypertension (32.5%), and hemorrhage (32.5%), mainly including gum bleeding and urethrorrhagia. AK109 exhibited an approximately linear PK exposure with dose escalation at 2-12 mg/kg. PD analyses showed rapid target engagement. Among the 40 patients, 4 achieved partial response and 21 achieved stable disease with an objective response rate of 10% and a disease control rate of 62.5%. Based on the safety profile, the PK/PD profile, and preliminary antitumor activities, 12 mg/kg Q2W and 15 mg/kg Q3W were selected as RP2D. AK109 showed manageable safety profile and promising antitumor activity, supporting further clinical development in a large population.

Design and Preliminary Performance Assessment of a PHM System for Electromechanical Flight Control Actuators

The evolution toward “more electric” aircraft has seen a decisive push in the last decade due to growing environmental concerns and the development of new market segments (flying taxis). Such a push has involved both the propulsion components and the aircraft systems, with the latter seeing a progressive trend in replacing traditional solutions based on hydraulic power with electrical or electromechanical devices. Flight Control Systems (FCSs) are one of the aircraft systems affected the most since the adoption of Electromechanical Actuators (EMAs) would provide several advantages over traditional electrohydraulic or mechanical solutions, but their application is still limited due to their sensitivity to certain single points of failure that can lead to mechanical jams. The development of an effective and reliable Prognostics and Health Management (PHM) system for EMAs could help in mitigating the risk of a sudden critical failure by properly recognizing and tracking the ongoing fault and anticipating its evolution, thus boosting the acceptance of EMAs as the primary flight-control actuators in commercial aircraft. The paper is focused on the results of the preliminary activities performed within the CleanSky 2/Astib research program, dedicated to the definition of the iron bird of a new regional-transport aircraft able to provide some prognostic capabilities and act as a technological demonstrator for new PHM strategies for EMAs employed in-flight control systems. The paper is organized as follows. At first, a proper introduction to the research program is provided, along with a brief description of the employed approach. Hence the simulation models adopted for the study are presented and used to build synthetic databases to inform the definition of the PHM algorithm. The prognostic framework is then presented, and a preliminary assessment of its expected performance is discussed.

Total syntheses of pongaflavone and its natural analogues

The efficient total synthesis of anti-tumor natural product pongaflavone (1) was described starting from commercially available 2,4-dihydroxyacetophenone (9) via seven steps and in 16% overall yield. Its two natural analogues pongachromene (2) and 7,8-(2”,2”-dimethylpyrano)-5,3’,4’-trihydroxy-3-methoxyflavone (3) were also synthesized following the similar procedure with the yields of 11% and 18%, respectively. Their preliminary anti-tumor activities were evaluated by the inhibition effect on A549 cells. The result showed that this kind of natural products exhibited different levels of anti-tumor activity. Among them, pongachromene (2) displayed the best anti-tumor activity.

STUDI DESKRIPTIF PELAKSANAAN PEMBELAJARAN DARING PADA KELAS RENDAH DI SEKOLAH DASAR NEGERI 04 SELUMA

This study aims to describe the process of implementation online learning in 1st, 2nd, and 3rd grades at SD Negeri 04 Seluma and the supporting and inhibiting factors. This research was a qualitative research with the phenomenological approach. The research subjects in this study were 1st, 2nd, and 3rd grade teachers and 1st, 2nd, and 3rd graders. The research instrument was the researcher himself using observation sheets, interviews, questionnaires, and documentation. The data analysis techniques data collection, data condensation, data presentation, and drawing conclusions. Techniques for validating data through extended observations, increasing persistence, as well as triangulation of sources and techniques. The results showed that the implementation of online learning in the 1st, 2nd, and 3rd grades consisted of preliminary activities, core activities, and closing activities. There are supporting factors for online learning, namely the availability of online learning support facilities in schools such as laptops and gadgets, the state internet network, the provision of internet quota from the Ministry of Education and Culture, and adequate textbooks. In addition, it was also found that the inhibiting factors for online learning were the lack of supervision of parents and teachers during online learning, the level of understanding of students was different, teachers were not fully ready to carry out online learning, not all students had devices for online learning. Based on the results of the study, it can be concluded that online learning at the 04 Seluma State Elementary School has been carried out in the lower class.

A Model Of Cultivating Morality In Fikih Learning Strategies Course

This study aims to find a model of instilling morals carried out by lecturers in the fiqh learning strategy course. This research uses a qualitative approach with a descriptive study method, meaning that the researcher describes the actual phenomena related to the model of inculcating morals in the lecture process. Collecting research data using the method of observation, interviews and documentation studies. Data analysis using data reduction techniques, data presentation, and drawing conclusions. The data sources for this research were lecturers of the science learning strategy course (key informants) and students (supporting informants) at FITK UIN North Sumatra Medan. Test the validity of the research using data triangulation techniques. The results of this study concluded that the model of inculcating morals was carried out effectively and on target by lecturers in the fiqh learning strategy course towards students. This is characterized by two aspects, namely (1) instilling morals in students is given in learning activities, including preliminary activities, core activities, and closing activities; and (2) moral values that are instilled in students include morals towards Allah SWT, morals towards Rasulullah SAW, morals to oneself, and morals to fellow human beings.

Penerapan Metode Cooperative Tipe Jigsaw dalam Meningkatkan Keaktifan Belajar Siswa Kelas V pada Pembelajaran Bahasa Indonesia di SD Negeri 03 Sidigede Kecamatan Welahan Kabupaten Jepara

Researchers focus on conducting research in increasing the activeness of learning using the Jigsaw Type Cooperative learning method in learning Indonesian. The research was conducted to 1) find out the process of learning activities with the jigsaw cooperative learning method to increase the learning activity of fifth grade students in learning Indonesian. 2) Knowing the application of the cooperative type jigsaw method in increasing the learning activity of fifth grade students in learning Indonesian. This research method uses a type of qualitative research with a qualitative descriptive approach. The data sources used are primary and secondary data sources. Data collection techniques used in this research are observation, interviews, documents, and documentation. As for testing the validity of the data using source triangulation, technical triangulation, and time triangulation. Furthermore, researchers used data analysis in the form of data reduction, data presentation (data display), and drawing conclusions. The results of this study indicate that (1) the process of learning activities of the jigsaw cooperative learning method in the Indonesian language subject at SD Negeri 03 Sidigede Welahan Jepara goes through the stages of preparing the teacher to prepare a Learning Implementation Plan (RPP) and implementing the learning process with explanations The material presented includes preliminary activities, core activities, closing activities, evaluation activities, and assessment activities. (2) In applying the jigsaw type cooperative learning method, the teacher provides mastery of the material to students, namely in the form of evaluating the questions in thematic books in groups. It can be seen in the application of the cooperative type jigsaw method at SD Negeri 03 Sidigede that students listen to discussions well, can know the abilities of each individual, during discussions students ask each other questions and opinions, all students play an active role, accept each other's deficiencies in differences of opinion from the results of their friends' answers, students dare to solve problems, deeper understanding, all students are enthusiastic about doing assignments.

Application of Education Management Information System in the Online Learning Process in Madrasah

Educational institutions will be more advanced and globally competitive with the ability to adapt to the application of management information systems which in the learning process are currently integrating online and offline learning. Therefore, schools must prepare strategies to deal with the negative impacts or problems that may occur from the application of management information systems in online learning. This study aims to analyze the application of management information systems in the online learning process. This type of research is descriptive qualitative research. Data collection techniques use observation, interviews and documentation. This data collection includes interviews, observations, documentation, and questionnaires. Data analysis techniques through data reduction, data presentation, qualitative data analysis, drawing conclusions and data validity. The results of the study explained that the implementation of the management information system using data processing applications, namely EMIS and information technology in supporting the learning process, providing educational services by facilitating learning practices using technological infrastructure, such as learning facilities by combining applications and computers with wifi. The implementation of learning through three stages, namely first, the planning stage by making an effective day analysis and analyzing the learning program by compiling a syllabus, compiling lesson plans, making learning media and preparing other learning tools. Second, the implementation stage, in the implementation stage there are three activities, namely preliminary activities, this activity, and closing activities. Third, evaluation of learning, at this stage assess student learning outcomes in writing, orally, scientific work, tasks and practice. In addition, the teacher makes direct observations to observe the attitudes of students in terms of spirituality, knowledge and skills. This research focuses on online learning where in its management it still takes various efforts to get the right and measurable formula, so that student learning outcomes can be achieved optimally

Implementasi Strategi Pembelajaran Berbasis Masalah Pada Mata Pelajaran PAI Kelas X Di SMAN 1 Kecamatan Kapur IX

The background of this research is that not all students can understand this problem-based learning, and also not all students are able to think actively in solving problems that occur. Students are less enthusiastic in participating in learning and students who play around or don't focus on learning. From the problems that exist, the researcher is interested in studying the application of problem-based learning in Islamic Religious Education Class X at SMAN 1 Kapur IX District and its inhibiting factors. This study aims to find out how the application of this problem-based learning strategy and its inhibiting factors. This type of research is a descriptive qualitative research that describes problem-based learning strategies in Islamic Religious Education Class X at SMAN 1 Kapur IX District. In collecting data researchers used observation techniques, interviews and documentation. Meanwhile, to analyze it, the researcher uses data reduction, data presentation and conclusion drawing. Based on the results of the research conducted, the authors found that Islamic Religious Education teachers apply problem-based learning strategies starting from teacher planning in preparing lessons by making lesson plans which serve as teacher guidelines in teaching and learning activities carried out in the classroom. The application of problem-based learning strategies is carried out through three activities, namely preliminary activities, core activities and closing activities. The activity starts from the teacher entering the class by greeting, conditioning the class and then praying together after that the teacher explains the indicators and learning objectives. The core activities of student learning are given related to learning problems then students will observe and find solutions to the problems that occur. Closing activities at the end with the teacher and concluding student lessons, giving assignments and praying together. The inhibiting factors found were time allocation, students who were less able to solve problems that occurred and students playing games during learning.