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Targeted degradation of cell surface and extracellular proteins via lysosomal delivery is an important means to modulate extracellular biology. However, these approaches have limitations due to lack of modularity, ease of development, restricted tissue targeting and applicability to both cell surface and extracellular proteins. We describe a lysosomal degradation strategy, termed cytokine receptor-targeting chimeras (KineTACs), that addresses these limitations. KineTACs are fully genetically encoded bispecific antibodies consisting of a cytokine arm, which binds its cognate cytokine receptor, and a target-binding arm for the protein of interest. We show that KineTACs containing the cytokine CXCL12 can use the decoy recycling receptor, CXCR7, to target a variety of target proteins to the lysosome for degradation. Additional KineTACs were designed to harness other CXCR7-targeting cytokines, CXCL11 and vMIPII, and the interleukin-2 (IL-2) receptor-targeting cytokine IL-2. Thus, KineTACs represent a general, modular, selective and simple genetically encoded strategy for inducing lysosomal delivery of extracellular and cell surface targets with broad or tissue-specific distribution.

Pelatihan dan Pendampingan Pembuatan Cerita Bergambar Berbasis Digital bagi Guru Sekolah Dasar di SDN Balasklumprik 1 Surabaya merupakan sebuah inisiatif yang bertujuan untuk meningkatkan kompetensi dan kreativitas guru dalam mengembangkan bahan ajar berbasis teknologi. Metode pelaksanaan yang digunakan pelatihan dan pendampingan. Pelatihan dilakukan melalui serangkaian sesi pembelajaran praktis tentang penggunaan perangkat lunak khusus untuk menciptakan cerita bergambar berbasis digital. Setelah pelatihan, guru-guru di SDN Balasklumprik 1 Surabaya diberikan pendampingan berkelanjutan dalam pengembangan cerita bergambar digital. Hasil penelitian menunjukkan bahwa pelatihan dan pendampingan ini telah memberikan dampak positif pada kemampuan guru dalam menciptakan cerita bergambar digital yang kreatif dan relevan dengan kurikulum sekolah dasar. Selain itu, guru juga mengalami peningkatan motivasi dan kepercayaan diri dalam mengintegrasikan teknologi dalam proses pembelajaran. Hasil ini menunjukkan bahwa pendekatan pelatihan dan pendampingan berbasis praktik sangat efektif dalam meningkatkan kompetensi guru dalam mengadopsi teknologi pendidikan. Penelitian ini memberikan kontribusi penting dalam mendukung pengembangan sumber daya manusia di bidang pendidikan, khususnya di tingkat sekolah dasar. Hasilnya dapat menjadi acuan bagi sekolah-sekolah dan lembaga pendidikan lainnya untuk mengembangkan program pelatihan dan pendampingan serupa guna memperkuat kompetensi guru dalam mengintegrasikan teknologi dalam proses pembelajaran. Selain itu, penelitian ini juga menggarisbawahi pentingnya kolaborasi antara pemerintah, sekolah, dan masyarakat dalam mendukung penggunaan teknologi dalam pendidikan. Abstract: Training and Mentoring for the Digital-based Illustrated Story Creation by Elementary School Teachers at SDN Balasklumprik 1 Surabaya is an initiative aimed at enhancing the competence and creativity of teachers in developing technology-based teaching materials. The impleme

Some parasitic diseases, such as malaria, require two hosts to complete their lifecycle: a human and an insect vector. Although most malaria research has focused on parasite development in the human host, the life cycle within the vector is critical for the propagation of the disease. The mosquito stage of the Plasmodium lifecycle represents a major demographic bottleneck, crucial for transmission blocking strategies. Furthermore, it is in the vector, where sexual recombination occurs generating “de novo” genetic diversity, which can favor the spread of drug resistance and hinder effective vaccine development. However, understanding of vector-parasite interactions is hampered by the lack of experimental systems that mimic the natural environment while allowing to control and standardize the complexity of the interactions. The breakthrough in stem cell technologies has provided new insights into human-pathogen interactions, but these advances have not been translated into insect models. Here, we review in vivo and in vitro systems that have been used so far to study malaria in the mosquito. We also highlight the relevance of single-cell technologies to progress understanding of these interactions with higher resolution and depth. Finally, we emphasize the necessity to develop robust and accessible ex vivo systems (tissues and organs) to enable investigation of the molecular mechanisms of parasite-vector interactions providing new targets for malaria control.

Monoclonal antibodies have created tremendous value for patients, with six of the top ten selling FDA approved drugs being monoclonal antibodies. Generally, monoclonal antibodies work by blocking protein function or inducing cell death via effector functions, such as antibody-dependent cellular toxicity. Though monoclonal antibodies have been greatly successful for various targets and diseases, some disease contexts could benefit from added functionality. For example, on-target, off-tumor toxicity is common when using a monoclonal antibody to target a disease protein that is also expressed on normal cells, as is the case with human epidermal growth factor receptor in breast cancer. Bispecific or bifunctional antibodies, which can recognize two different antigens or have dual functionalities, have the potential to offer greater selectivity, efficacy, and functionality compared to monoclonal antibodies. Various forms of bispecific antibodies exist to date, including bispecific IgGs, which add disease specificity by targeting a disease-specific protein and the target protein simultaneously, bispecific T cell engagers, which enable recruitment of cytotoxic T cells to tumor cells, and antibody-drug conjugates, which involve the tumor specific delivery of a highly cytotoxic small molecule payload using antibody-induced receptor internalization. Here, I describe three novel approaches using bifunctional antibody-based technologies. In Chapter 1, I describe the use of bispecific antibody-cytokine fusions, termed KineTACs, which can be applied as a novel strategy for the targeted degradation of cell surface and extracellular proteins. In Chapter 2, I highlight an orthogonal targeted degradation approach using antibody-drug conjugates in which the antibody recruits a cell surface E3 ligase, and the small molecule binds a cell surface multi-pass membrane protein, enabling its degradation. In Chapter 3, I describe the use of bispecific VH-Fab IgGs targeting different epitopes o

Monoclonal antibodies have created tremendous value for patients, with six of the top ten selling FDA approved drugs being monoclonal antibodies. Generally, monoclonal antibodies work by blocking protein function or inducing cell death via effector functions, such as antibody-dependent cellular toxicity. Though monoclonal antibodies have been greatly successful for various targets and diseases, some disease contexts could benefit from added functionality. For example, on-target, off-tumor toxicity is common when using a monoclonal antibody to target a disease protein that is also expressed on normal cells, as is the case with human epidermal growth factor receptor in breast cancer. Bispecific or bifunctional antibodies, which can recognize two different antigens or have dual functionalities, have the potential to offer greater selectivity, efficacy, and functionality compared to monoclonal antibodies. Various forms of bispecific antibodies exist to date, including bispecific IgGs, which add disease specificity by targeting a disease-specific protein and the target protein simultaneously, bispecific T cell engagers, which enable recruitment of cytotoxic T cells to tumor cells, and antibody-drug conjugates, which involve the tumor specific delivery of a highly cytotoxic small molecule payload using antibody-induced receptor internalization. Here, I describe three novel approaches using bifunctional antibody-based technologies. In Chapter 1, I describe the use of bispecific antibody-cytokine fusions, termed KineTACs, which can be applied as a novel strategy for the targeted degradation of cell surface and extracellular proteins. In Chapter 2, I highlight an orthogonal targeted degradation approach using antibody-drug conjugates in which the antibody recruits a cell surface E3 ligase, and the small molecule binds a cell surface multi-pass membrane protein, enabling its degradation. In Chapter 3, I describe the use of bispecific VH-Fab IgGs targeting different epitopes o

Siswa sekolah dasar sangat terpukul oleh pandemi Covid-19, yang telah mempengaruhi hampir setiap bidang kehidupan mereka. Ada kebutuhan untuk menemukan model pembelajaran alternatif yang memadai dan relevan dengan fitur siswa dan dapat digunakan dalam keadaan terbatas seperti flipped learning. Sebagai bagian dari kontribusi masyarakat ini, Madrasah Ibtidaiyah telah diberi kesempatan untuk menerapkan pembelajaran terbalik sehingga sekolah lain, seperti itu, memiliki kesempatan yang sama untuk mempromosikan pembelajaran yang sukses. Teori flipped learning diperkenalkan pada hari pertama kebaktian ini, yang berlangsung selama dua hari. Sebagai bagian dari layanan ini, peserta pelatihan memiliki pilihan untuk membuat video instruksional yang akan digunakan. Untuk mengintegrasikan flipped learning di madrasah, guru mendampingi seluruh komponen pembelajaran. Menurut rata-rata skor pre-test 40 sampai 70, meningkat 30 persen, pengetahuan guru tentang flipped learning meningkat secara signifikan. Akibatnya, tidak hanya guru yang lebih mampu memahami murid mereka, tetapi siswa dan guru sama-sama mendapatkan perspektif dan perspektif baru tentang pembelajaran secara keseluruhan.

The spread of COVID-19 has made it difficult to teach in the classroom. One way to avoid this challenge is through online virtual classes. consequently, the media must play a role in ensuring that students are engaged in their studies. This community service aims to empower Powtoon in virtual learning at SDN Curahsawo 3, Probolinggo Regency. The PKM project is designed to help teachers use technology more effectively when creating instructional videos that can be used during the learning process. This community service project is divided into four parts: observation, looking at the problem, looking for solutions, and finding. This service involves 28 first graders. Adopting Powtoon media has many benefits, such as increasing student enthusiasm, making learning more interesting, and helping students learn faster. In addition, the teacher's enthusiasm for developing Powtoon content is evident. Abstrak: Penyebaran COVID-19 telah membuat sulit untuk mengajar di kelas. Salah satu cara untuk menghindari tantangan ini adalah melalui kelas virtual online. Akibatnya, media harus memainkan peran dalam memastikan bahwa siswa terlibat dalam studi mereka. Pengabdian masyarakat ini bertujuan untuk memberdayakan powtoon dalam pembelajaran virtual di SDN Curahsawo 3 Kabupaten Probolinggo. Proyek PKM dirancang untuk membantu guru menggunakan teknologi secara lebih efektif ketika membuat video pembelajaran yang dapat digunakan selama proses pembelajaran. Proyek pengabdian masyarakat ini dibagi menjadi empat bagian: observasi, melihat masalah, mencari solusi, dan mengevaluasi. Layanan ini melibatkan 28 siswa kelas satu. Mengadopsi media Powtoon memiliki banyak manfaat, seperti meningkatkan semangat siswa, membuat pembelajaran lebih menarik, dan membantu siswa belajar lebih cepat. Selain itu, antusiasme guru untuk mengembangkan konten Powtoon terlihat jelas.

KKG 28 di Kecamatan Rowokangkung Kabupaten Lumajang, Indonesia, Mita PKM memiliki masalah dengan temuan cara baru untuk mengajar dan belajar dan kurangnya pemahaman dari pihak guru tentang pendidikan digital. Tujuan dari yang kami lakukan di sini adalah membantu KKG dalam mengembangkan kualitas pembelajaran melalui metode pengajaran dan pembelajaran yang inovatif dan literasi digital. Untuk melaksanakan hal tersebut dilakukan workshop. Kedua pendekatan ini, yaitu teoritis dan praktis, digabungkan. Menggunakan kahoot sebagai contoh model pembelajaran inovatif, tulisan ini mengambil pendekatan teoritis. Menggunakan kahoot, model pembelajaran inovatif, pendekatan praktis digunakan untuk menyusun rencana pembelajaran (RPP). Ditemukan bahwa keikutsertaan dalam kegiatan ini meningkatkan pengetahuan guru tentang model pembelajaran baru dan kemampuan mereka untuk menciptakannya, serta kemampuan mereka untuk membuat rencana pembelajaran (RPP). Ditemukan juga bahwa kemampuan guru untuk menggunakan model pembelajaran baru ditingkatkan melalui penggunaan pembelajaran digital berbasis game.

The spread of COVID-19 has made it difficult to teach in the classroom. One way to avoid this challenge is through online virtual classes. consequently, the media must play a role in ensuring that students are engaged in their studies. This community service aims to empower Powtoon in virtual learning at SDN Curahsawo 3, Probolinggo Regency. The PKM project is designed to help teachers use technology more effectively when creating instructional videos that can be used during the learning process. This community service project is divided into four parts: observation, looking at the problem, looking for solutions, and finding. This service involves 28 first graders. Adopting Powtoon media has many benefits, such as increasing student enthusiasm, making learning more interesting, and helping students learn faster. In addition, the teacher's enthusiasm for developing Powtoon content is evident. Abstrak: Penyebaran COVID-19 telah membuat sulit untuk mengajar di kelas. Salah satu cara untuk menghindari tantangan ini adalah melalui kelas virtual online. Akibatnya, media harus memainkan peran dalam memastikan bahwa siswa terlibat dalam studi mereka. Pengabdian masyarakat ini bertujuan untuk memberdayakan powtoon dalam pembelajaran virtual di SDN Curahsawo 3 Kabupaten Probolinggo. Proyek PKM dirancang untuk membantu guru menggunakan teknologi secara lebih efektif ketika membuat video pembelajaran yang dapat digunakan selama proses pembelajaran. Proyek pengabdian masyarakat ini dibagi menjadi empat bagian: observasi, melihat masalah, mencari solusi, dan mengevaluasi. Layanan ini melibatkan 28 siswa kelas satu. Mengadopsi media Powtoon memiliki banyak manfaat, seperti meningkatkan semangat siswa, membuat pembelajaran lebih menarik, dan membantu siswa belajar lebih cepat. Selain itu, antusiasme guru untuk mengembangkan konten Powtoon terlihat jelas.

Learning during the COVID-19 pandemic requires all educators to be more creative and innovative in packaging subject matter. The subject matter presented is not only interesting but also must be able to maximize the competencies possessed by students. Therefore, learning materials must be made very pleasant and easy to understand. The purpose of this Community Service (PPM) activity is to provide elementary school teachers with skills and insight in creating simple and interesting children's songs according to the theme of the lesson in elementary school, so that students can be more interested and easily understand the material presented by the teacher. The method used in this activity is training and mentoring which is carried out online with the target subject of 73 elementary school teachers in Magetan. The stages of training activities include working on pre-test questions, explaining song creation material, practicing individual children's song creations, assisting in creating children's songs via WhatsApp, Telegram groups and Google Drive, presenting the results of song creation followed by evaluation of the next activity working on post-test questions. The result of the implementation of training and mentoring activities is that elementary school teachers can better understand how to make children's songs according to simple, easy and interesting lesson themes. This can be seen from the results of making song lyrics that are in accordance with the theme of the lesson, making good tones that are created by themselves or using existing tones and being able to sing songs that have been created. The conclusion is that the training and mentoring activities for the creation of thematic children's songs have been carried out well and provide benefits to elementary school teachers. It is hoped that similar activities can continue to be carried out in order to increase teacher creativity.

KKG 28 di Kecamatan Rowokangkung Kabupaten Lumajang, Indonesia, Mita PKM memiliki masalah dengan temuan cara baru untuk mengajar dan belajar dan kurangnya pemahaman dari pihak guru tentang pendidikan digital. Tujuan dari yang kami lakukan di sini adalah membantu KKG dalam mengembangkan kualitas pembelajaran melalui metode pengajaran dan pembelajaran yang inovatif dan literasi digital. Untuk melaksanakan hal tersebut dilakukan workshop. Kedua pendekatan ini, yaitu teoritis dan praktis, digabungkan. Menggunakan kahoot sebagai contoh model pembelajaran inovatif, tulisan ini mengambil pendekatan teoritis. Menggunakan kahoot, model pembelajaran inovatif, pendekatan praktis digunakan untuk menyusun rencana pembelajaran (RPP). Ditemukan bahwa keikutsertaan dalam kegiatan ini meningkatkan pengetahuan guru tentang model pembelajaran baru dan kemampuan mereka untuk menciptakannya, serta kemampuan mereka untuk membuat rencana pembelajaran (RPP). Ditemukan juga bahwa kemampuan guru untuk menggunakan model pembelajaran baru ditingkatkan melalui penggunaan pembelajaran digital berbasis game.

Learning during the COVID-19 pandemic requires all educators to be more creative and innovative in packaging subject matter. The subject matter presented is not only interesting but also must be able to maximize the competencies possessed by students. Therefore, learning materials must be made very pleasant and easy to understand. The purpose of this Community Service (PPM) activity is to provide elementary school teachers with skills and insight in creating simple and interesting children's songs according to the theme of the lesson in elementary school, so that students can be more interested and easily understand the material presented by the teacher. The method used in this activity is training and mentoring which is carried out online with the target subject of 73 elementary school teachers in Magetan. The stages of training activities include working on pre-test questions, explaining song creation material, practicing individual children's song creations, assisting in creating children's songs via WhatsApp, Telegram groups and Google Drive, presenting the results of song creation followed by evaluation of the next activity working on post-test questions. The result of the implementation of training and mentoring activities is that elementary school teachers can better understand how to make children's songs according to simple, easy and interesting lesson themes. This can be seen from the results of making song lyrics that are in accordance with the theme of the lesson, making good tones that are created by themselves or using existing tones and being able to sing songs that have been created. The conclusion is that the training and mentoring activities for the creation of thematic children's songs have been carried out well and provide benefits to elementary school teachers. It is hoped that similar activities can continue to be carried out in order to increase teacher creativity.

Because of the Covid-19 epidemic, the learning method in primary schools has shifted from conventional learning to virtual learning, which is more effective. One of the challenges elementary school instructors face is the usage of virtual learning apps that are appealing to pupils. Virtual learning applications are becoming more popular. This service activity is a training session for teachers at SDN Tambelang 1 in Probolinggo Regency on how to utilize the Quizziz and Wordwall programs in the classroom to enhance learning. The participants in this activity will be 11 teachers who will be service partners with the organization. The Zoom platform is used for all of the activities that take place online. The exercise is divided into two stages: the first stage involves the presentation of content and practice with the Quizizz program, and the second stage involves the presentation of material and practice with the Wordwall application, respectively. Techniques for gathering information with surveys or questionnaires. The average participant answer was utilized in the data analysis. The replies of participants revealed that instructors developed knowledge and abilities in the use of the Quizizz and Wordwall programs, which was a good outcome. The inability of the internet network to function properly is a stumbling block in this endeavour. Abstrak: Karena wabah Covid-19, metode pembelajaran di sekolah dasar telah bergeser dari pembelajaran konvensional ke pembelajaran virtual yang lebih efektif. Salah satu tantangan yang dihadapi guru sekolah dasar adalah penggunaan aplikasi pembelajaran virtual yang menarik bagi siswa. Aplikasi pembelajaran virtual menjadi lebih populer. Kegiatan pengabdian ini merupakan sesi pelatihan bagi para guru di SDN Tambelang 1 Kabupaten Probolinggo tentang bagaimana memanfaatkan program Quizziz dan Wordwall di dalam kelas untuk meningkatkan pembelajaran. Peserta dalam kegiatan ini adalah 11 orang guru yang akan menjadi mitra pengabdian organi

Mengidentifikasi dan memperoleh informasi tentang kendala proses adalah tujuan dari penelitian ini. Penelitian ini menggunakan metode studi kasus deskriptif untuk mengumpulkan data tentang keterbatasan dan dampak program COVID-19 terhadap proses belajar mengajar di sekolah dasar. Menggunakan literatur yang relevan, kami menghasilkan daftar pertanyaan untuk ditanyakan dalam wawancara semi-terstruktur. Guru, orang tua, dan anak-anak dari sebuah sekolah dasar di Kabupaten Probolinggo berpartisipasi dalam penelitian ini. Studi ini menemukan bahwa siswa, guru, dan orang tua menghadapi sejumlah tantangan dalam kegiatan belajar mengajar internet, antara lain kurangnya keahlian teknologi, masuknya biaya kuota online, adanya pekerjaan tambahan bagi orang tua dalam membantu siswanya dalam belajar. proses, interaksi dan interaksi interpersonal antara siswa, guru, dan orang tua berkurang, dan jam kerja menjadi tidak terbatas bagi guru karena harus berkomunikasi dengan siswa, guru, dan orang tua.

Many elementary school students consider mathematics to be the most difficult and complicated subject. Thus, students must be able to understand mathematics learning because mathematics is a means to solve everyday problems such as reading and writing. Difficulties in learning mathematics in understanding concepts must be given a solution as early as possible, otherwise students will face many problems in the future because almost all fields of study require proper mathematics. One of the factors causing learning difficulties is learning motivation and interest in learning mathematics, the low motivation and interest in learning mathematics is due to the lack of precise learning methods used in learning mathematics. Every concept or principle in mathematics that is presented in a concrete form will be well understood by students. The formation of mathematical concepts can be achieved through a series of interconnected patterns in a sequence of planned learning activities between the knowledge structure section and an active learner, using special media designed for mathematics learning. The purpose of this activity is to introduce a mathematics learning method which is the development of the dienes learning theory, namely the BEBER method, namely playing while learning mathematics. Abstrak: Banyak siswa sekolah dasar yang menganggap matematika sebagai pembelajaran yang paling sulit dan rumit. Dengan demikian, siswa harus dapat memahami pembelajaran matematika karena matematika merupakan sarana untuk memecahkan masalah sehari-hari seperti halnya membaca dan menulis. Kesulitan belajar matematika dalam memahami konsep harus diberikan solusi sedini mungkin, kalau tidak siswa akan menghadapi banyak masalah kedepannya karena hampir semua bidang studi membutuhkan matematika yang tepat. Salah satu faktor penyebab kesulitan belajar adalah motivasi belajar dan minat belajar matematika, rendahnya motivasi dan minat belajar matematika disebabkan karena kurang tepatnnya metode p

Kegiatan Pengabdian Kepada Masyarakat (PKM) bertujuan untuk memberikan pelatihan kepada calon guru tentang pembuatan e-modul berbasis android. Metode pelatihan terdiri dari tiga tahap yairu tahap persiapan, tahap pelaksanaan dan tahap evaluasi. Tahap persiapan melakukan survey terhadap kebutuhan calon guru mengenai perangkat pembelajaran, tahap pelaksanaan yaitu melakukan pelatihan pembuaan e-modul berbasis android sementara untuk tahap evaluasi dilakukan dengan cara memberikan angket kepuasan terhadap pelaksanaan pelatihan kepada semua peserta pelatihan. Instrumen penelitian mengggunakan angket dengan analisis data berupa persentase kepuasan terhadap pelatihan. Hasil yang diperoleh bahwa peserta pelatihan merasa sangat puas dengan kegiatan pelatihan ditinjau dari sisi persiapan acara, materi, kegiatan pelatihan, dan pelayanan konsumsi.

Maarif NU Educational Institution of Surabaya City houses several schools and there are still many teachers who do not understand theoretically and practically the policy of freedom of learning, even though the teacher's understanding of curriculum reform is very essential. Teachers find it difficult to implement a policy of fredom of learning at school and in the classroom. Teachers have difficulty in developing learning methods referring to independent learning. In addition, teachers have difficulty developing an fredom of learning curriculum (just curriculum transmitter). We provide training and mentoring to teachers for three meetings intensively. The result is an increase in teacher understanding in three aspects; (1), theoretically, (2), how to implement it, and (3), how to develop curriculum. This means that training and mentoring is very important to be carried out by more competent experts. This is in line with the research by Postholm (2012), which states that it is important for teacher training to be carried out by more competent people to increase teachers' understanding of the curriculum.Abstrak: Lembaga Pendidikan Maarif NU Kota Surabaya menaungi beberapa sekolah. Namun sumber daya manusia yang dimiliki masih terbatas serta fasilitas yang dimiliki juga masih relatif terbatas. Masih banyak guru yang belum memahami secara teoretis dan praktis kebijakan merdeka belajar padahal pemahaman guru terhadap reformasi kurikulum sangat esensial. Guru merasa kesulitan menerapkan kebijakan merdeka belajar di sekolah dan di kelas. Guru kesulitan dalam mengembangkan metode pembelajaran merujuk pada merdeka belajar. Selain itu guru kesulitan mengembangkan kurikulum merdeka belajar (curriculum transmitter). Kami memberikan pelatihan dan pendampingan kepada guru-guru selama tiga kali pertemuan dengan intensif. Hasilnya terjadi peningkatan pemahaman guru dalam tiga aspek; (1), secara teoretis, (2), bagaimana mengimplementasikannya, dan (3), bagaimana mengembangkan kuriku

Because of the Covid-19 epidemic, the learning method in primary schools has shifted from conventional learning to virtual learning, which is more effective. One of the challenges elementary school instructors face is the usage of virtual learning apps that are appealing to pupils. Virtual learning applications are becoming more popular. This service activity is a training session for teachers at SDN Tambelang 1 in Probolinggo Regency on how to utilize the Quizziz and Wordwall programs in the classroom to enhance learning. The participants in this activity will be 11 teachers who will be service partners with the organization. The Zoom platform is used for all of the activities that take place online. The exercise is divided into two stages: the first stage involves the presentation of content and practice with the Quizizz program, and the second stage involves the presentation of material and practice with the Wordwall application, respectively. Techniques for gathering information with surveys or questionnaires. The average participant answer was utilized in the data analysis. The replies of participants revealed that instructors developed knowledge and abilities in the use of the Quizizz and Wordwall programs, which was a good outcome. The inability of the internet network to function properly is a stumbling block in this endeavour. Abstrak: Karena wabah Covid-19, metode pembelajaran di sekolah dasar telah bergeser dari pembelajaran konvensional ke pembelajaran virtual yang lebih efektif. Salah satu tantangan yang dihadapi guru sekolah dasar adalah penggunaan aplikasi pembelajaran virtual yang menarik bagi siswa. Aplikasi pembelajaran virtual menjadi lebih populer. Kegiatan pengabdian ini merupakan sesi pelatihan bagi para guru di SDN Tambelang 1 Kabupaten Probolinggo tentang bagaimana memanfaatkan program Quizziz dan Wordwall di dalam kelas untuk meningkatkan pembelajaran. Peserta dalam kegiatan ini adalah 11 orang guru yang akan menjadi mitra pengabdian organi

Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angiotensin-converting enzyme 2 (ACE2) binding interface of the SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified VH binders to two non-overlapping epitopes and further assembled these into multivalent and bi-paratopic formats. These VH constructs showed increased affinity to Spike (up to 600-fold) and neutralization potency (up to 1,400-fold) on pseudotyped SARS-CoV-2 virus when compared to standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with a half-maximal inhibitory concentration (IC50) of 4.0 nM (180 ng ml-1). A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain engaging an RBD at the ACE2 binding site, confirming our original design strategy.

Numerous neutralizing antibodies that target SARS-CoV-2 have been reported, and most directly block binding of the viral Spike receptor-binding domain (RBD) to angiotensin-converting enzyme II (ACE2). Here, we deliberately exploit non-neutralizing RBD antibodies, showing they can dramatically assist in neutralization when linked to neutralizing binders. We identified antigen-binding fragments (Fabs) by phage display that bind RBD, but do not block ACE2 or neutralize virus as IgGs. When these non-neutralizing Fabs were assembled into bispecific VH/Fab IgGs with a neutralizing VH domain, we observed a ~ 25-fold potency improvement in neutralizing SARS-CoV-2 compared to the mono-specific bi-valent VH-Fc alone or the cocktail of the VH-Fc and IgG. This effect was epitope-dependent, reflecting the unique geometry of the bispecific antibody toward Spike. Our results show that a bispecific antibody that combines both neutralizing and non-neutralizing epitopes on Spike-RBD is a promising and rapid engineering strategy to improve the potency of SARS-CoV-2 antibodies.

Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angiotensin-converting enzyme 2 (ACE2) binding interface of the SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified VH binders to two non-overlapping epitopes and further assembled these into multivalent and bi-paratopic formats. These VH constructs showed increased affinity to Spike (up to 600-fold) and neutralization potency (up to 1,400-fold) on pseudotyped SARS-CoV-2 virus when compared to standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with a half-maximal inhibitory concentration (IC50) of 4.0 nM (180 ng ml-1). A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain engaging an RBD at the ACE2 binding site, confirming our original design strategy.

Numerous neutralizing antibodies that target SARS-CoV-2 have been reported, and most directly block binding of the viral Spike receptor-binding domain (RBD) to angiotensin-converting enzyme II (ACE2). Here, we deliberately exploit non-neutralizing RBD antibodies, showing they can dramatically assist in neutralization when linked to neutralizing binders. We identified antigen-binding fragments (Fabs) by phage display that bind RBD, but do not block ACE2 or neutralize virus as IgGs. When these non-neutralizing Fabs were assembled into bispecific VH/Fab IgGs with a neutralizing VH domain, we observed a ~ 25-fold potency improvement in neutralizing SARS-CoV-2 compared to the mono-specific bi-valent VH-Fc alone or the cocktail of the VH-Fc and IgG. This effect was epitope-dependent, reflecting the unique geometry of the bispecific antibody toward Spike. Our results show that a bispecific antibody that combines both neutralizing and non-neutralizing epitopes on Spike-RBD is a promising and rapid engineering strategy to improve the potency of SARS-CoV-2 antibodies.

Current serology tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies mainly take the form of enzyme-linked immunosorbent assays, chemiluminescent microparticle immunoassays or lateral flow assays, which are either laborious, expensive or lacking sufficient sensitivity and scalability. Here we present the development and validation of a rapid, low-cost, solution-based assay to detect antibodies in serum, plasma, whole blood and to a lesser extent saliva, using rationally designed split luciferase antibody biosensors. This new assay, which generates quantitative results in 30 min, substantially reduces the complexity and improves the scalability of coronavirus disease 2019 (COVID-19) antibody tests. This assay is well-suited for point-of-care, broad population testing, and applications in low-resource settings, for monitoring host humoral responses to vaccination or viral infection.

Actin plays fundamental roles in both the cytoplasm and the cell nucleus. In the nucleus, beta-actin regulates neuronal reprogramming by consolidating a heterochromatin landscape required for transcription of neuronal gene programs, yet it remains unknown whether it has a role in other differentiation models. To explore the potential roles of beta-actin in osteogenesis, beta-actin wild-type (WT) and beta-actin knockout (KO) mouse embryonic fibroblasts (MEFs) are reprogrammed to osteoblast-like cells using small molecules in vitro. It is discovered that loss of beta-actin leads to an accelerated mineralization phenotype (hypermineralization), accompanied with enhanced formation of extracellular hydroxyapatite microcrystals, which originate in the mitochondria in the form of microgranules. This phenotype is a consequence of rapid upregulation of mitochondrial genes including those involved in oxidative phosphorylation (OXPHOS) in reprogrammed KO cells. It is further found that osteogenic gene programs are differentially regulated between WT and KO cells, with clusters of genes exhibiting different temporal expression patterns. A novel function for beta-actin in osteogenic reprogramming through a mitochondria-based mechanism that controls cell-mediated mineralization is proposed.

Spiradenoma and cylindroma are distinctive skin adnexal tumors with sweat gland differentiation and potential for malignant transformation and aggressive behaviour. We present the genomic analysis of 75 samples from 57 representative patients including 15 cylindromas, 17 spiradenomas, 2 cylindroma–spiradenoma hybrid tumors, and 24 low- and high-grade spiradenocarcinoma cases, together with morphologically benign precursor regions of these cancers. We reveal somatic or germline alterations of the CYLD gene in 15/15 cylindromas and 5/17 spiradenomas, yet only 2/24 spiradenocarcinomas. Notably, we find a recurrent missense mutation in the kinase domain of the ALPK1 gene in spiradenomas and spiradenocarcinomas, which is mutually exclusive from mutation of CYLD and can activate the NF-κB pathway in reporter assays. In addition, we show that high-grade spiradenocarcinomas carry loss-of-function TP53 mutations, while cylindromas may have disruptive mutations in DNMT3A. Thus, we reveal the genomic landscape of adnexal tumors and therapeutic targets., SCOPUS: ar.j, info:eu-repo/semantics/published

Music education in Europe reflects the colorful diversity and rich tradition of the cultural identities of our continent. Within the music education landscape music schools are institutions specially focused on the practices of music-making. The First European Music School Symposium, which took place at the University of Music and Performing Arts Vienna in October 2017, brought together more than 150 researchers and practitioners from twenty-five European countries. The two cooperating partners, European Music School Union and Austrian Conference of Music School Associations, ensured a lively exchange between research and practitioners. This post-symposium publication presents contributions from twenty-nine researchers from thirteen European countries and paints a multicolored picture of music schools in Europe.

Music education in Europe reflects the colorful diversity and rich tradition of the cultural identities of our continent. Within the music education landscape music schools are institutions specially focused on the practices of music-making. The First European Music School Symposium, which took place at the University of Music and Performing Arts Vienna in October 2017, brought together more than 150 researchers and practitioners from twenty-five European countries. The two cooperating partners, European Music School Union and Austrian Conference of Music School Associations, ensured a lively exchange between research and practitioners. This post-symposium publication presents contributions from twenty-nine researchers from thirteen European countries and paints a multicolored picture of music schools in Europe.

Bioluminescence is a phenomenon that has fascinated mankind for centuries. Today the phenomenon and its sibling, chemiluminescence, have impacted society with a number of useful applications in fields like analytical chemistry and medicine, just to mention two. In this review, a molecular-orbital perspective is adopted to explain the chemistry behind chemiexcitation in both chemi- and bioluminescence. First, the uncatalyzed thermal dissociation of 1,2-dioxetane is presented and analyzed to explain, for example, the preference for triplet excited product states and increased yield with larger nonreactive substituents. The catalyzed fragmentation reaction and related details are then exemplified with substituted 1,2-dioxetanone species. In particular, the preference for singlet excited product states in that case is explained. The review also examines the diversity of specific solutions both in Nature and in artificial systems and the difficulties in identifying the emitting species and unraveling the color modulation process. The related subject of excited-state chemistry without light absorption is finally discussed. The content of this review should be an inspiration to human design of new molecular systems expressing unique light-emitting properties. An appendix describing the state-of-the-art experimental and theoretical methods used to study the phenomena serves as a complement., PMID: 29493234

The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.

The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.

The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.

The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.

The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.

There are many composers from the Republic of Macedonia creating powerful musical pieces for the clarinet. The author has discovered 25 little-known works, which are performed mostly in Macedonia, including six clarinet solos, nine for clarinet and piano, and ten chamber works up to four players. Most valuable compositions from these works would include: Mariana (2005) by Ljubomir Branjolica, Sonata in Es (1972) by Blagoj Canev, Rondo Dramatico (1965) by Stojan Stojkov, Ludium & Fugue (2014) by Bojana Petrovic Aleksova, Suite from the Ballet Dubrovacka Legenda (1989) by Ljubomir Branjolica, Trio in As (1991) by Blagoj Canev, Trio Sonoro (1965) by Vlastimir Nikolovski, and Tomislav Zogravski’s 5 Pieces for clarinet Op. 131 (1997). The majority of compositions discovered are unknown in the United States. These works are written in a wide spectrum of compositional styles including neo-classical, folk, twelve-tone serialism, avant-garde, and atonal. This document includes an overview of the history of Macedonian music and its culture. It provides the biographies of the composers, their education, list of works that include the clarinet, achievements and awards, and places where their works have been performed. The annotated bibliography includes works for solo unaccompanied clarinet, clarinet and piano, clarinet and orchestra, and chamber music for up to four players. The entry for each work covers the following information: composer name, composer dates, title of the work and movements, date of composition, instrumentation, publisher and date of publication, and sources from which the music score and parts can be acquired. Further details include inspiration for each work, first performance and instrumentalist(s), range of clarinet writing, extended techniques used, basic form and stylistic characteristics of composition, and level of difficulty. It is hoped that this document will inspire the reader to appreciate the rich musical heritage of Macedonia and to encourage

A paradigm shift from hard to flexible, organic-based optoelectronics requires fast and reversible mechanical response from actuating materials that are used for conversion of heat or light into mechanical motion. As the limits in the response times of polymer-based actuating materials are reached, which are inherent to the less-than-optimal coupling between the light/heat and mechanical energy in them, a conceptually new approach to mechanical actuation is required to leapfrog the performance of organic actuators. Herein, we explore single crystals of 1,2,4,5-tetrabromobenzene (TBB) as actuating elements and establish relations between their kinematic profile and mechanical properties. Centimeter-size acicular crystals of TBB are the only naturally twinned crystals out of about a dozen known materials that exhibit the thermosalient effect - an extremely rare and visually impressive crystal locomotion. When taken over a phase transition, crystals of this material store mechanical strain and are rapidly self-actuated to sudden jumps to release the internal strain, leaping up to several centimeters. To establish the structural basis for this colossal crystal motility, we investigated the mechanical profile of the crystals from macroscale, in response to externally induced deformation under microscope, to nanoscale, by using nanoindentation. Kinematic analysis based on high-speed recordings of over 200 twinned TBB crystals exposed to directional or nondirectional heating unraveled that the crystal locomotion is a kinematically complex phenomenon that includes at least six kinematic effects. The nanoscale tests confirm the highly elastic nature, with an elastic deformation recovery (60%) that is far superior to those of molecular crystals reported earlier. This property appears to be critical for accumulation of stress required for crystal jumping. Twinned crystals of TBB exposed to moderate directional heating behave as all-organic analogue of a bimetallic strip, where

A complete understanding of the physics underlying the varied colors of firefly bioluminescence remains elusive because it is difficult to disentangle different enzyme-lumophore interactions. Experiments on isolated ions are useful to establish a proper reference when there are no microenvironmental perturbations. Here, we use action spectroscopy to compare the absorption by the firefly oxyluciferin lumophore isolated in vacuo and complexed with a single water molecule. While the process relevant to bioluminescence within the luciferase cavity is light emission, the absorption data presented here provide a unique insight into how the electronic states of oxyluciferin are altered by microenvironmental perturbations. For the bare ion we observe broad absorption with a maximum at 548 +/- 10 nm, and addition of a water molecule is found to blue-shift the absorption by approximately 50 nm (0.23 eV). Test calculations at various levels of theory uniformly predict a blue-shift in absorption caused by a single water molecule, but are only qualitatively in agreement with experiment highlighting limitations in what can be expected from methods commonly used in studies on oxyluciferin. Combined molecular dynamics simulations and time-dependent density functional theory calculations closely reproduce the broad experimental peaks and also indicate that the preferred binding site for the water molecule is the phenolate oxygen of the anion. Predicting the effects of microenvironmental interactions on the electronic structure of the oxyluciferin anion with high accuracy is a nontrivial task for theory, and our experimental results therefore serve as important benchmarks for future calculations., Funding Agencies|Lundbeckfonden||Human Frontier Science Project|RGY0081/2011|Kyoto Universitys Hakubi Project||Portuguese Foundation for Science and Technology|PTDC/FIS/103587/2008|Swedish Research Council|621-2010-5014|SERC (Swedish e-Science Research Center)

The anonymous channels have been the essence of numerous protocols that include anonymous message passing between peers. The mixnet structure is one way to accomplish the anonymity . Since the publication of the Chaumian mixnet, there have been many practical implementations. There are two main approaches to implement mixnets: the decryption (Chaumian) and the re-encryption mixnets. In this paper we analyze four types of mixnets, from which one decryption and three re-encryption types. They were implemented in the Java programing language and evaluated on several criterias as: the number of messages, the total number of nodes, the number of threshold nodes, and the key length of underlying crypto system. In the results section we compare the results from the practical tests to answer the research question, which type of mixnets has better features.

We study how probabilistic reasoning and inductive querying can be combined within ProbLog, a recent probabilistic extension of Prolog. ProbLog can be regarded as a database system that supports both probabilistic and inductive reasoning through a variety of querying mechanisms. After a short introduction to ProbLog, we provide a survey of the different types of inductive queries that ProbLog supports, and show how it can be applied to the mining of large biological networks.

Godkänd; 2009; 20091113 (ysko)

Godkänd; 2009; 20091113 (ysko)

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1111202%5DMICH-V-1111202, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1111202/MICH-V-1111202/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1111202%5DMICH-V-1111202, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1111202/MICH-V-1111202/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Comprend : Le Théâtre considéré comme moyen révolutionnaire, Avec mode texte

Thermosalient crystals are solids that exhibit motion at the macroscale as a consequence of a thermally induced phase transition. They represent an interesting scientific phenomenon and could be useful as actuators for the conversion of thermal energy into motion or mechanical work. The potential utilization of these miniature transducers in real-world devices requires a controllable phase transition (i.e. a predetermined temperature). While it is difficult to control these performances with a single-component molecular crystal, “tunable” properties could be accomplished by solid solutions. To verify this hypothesis, the thermosalient material [Zn(bpy)Br2] (bpy = 2,2′-bipyridine) was selected and its synthesis was performed in the presence of chloride ions. The resulting mixed crystals ([Zn(bpy)Br2xCl2(1−x)]) show that the product undergoes the expected thermosalient phase transition, and the temperature of the onset of the phase transition and the transition enthalpy depend on the Cl/Br ratio.

Plasmodium falciparum secretes extracellular vesicles (PfEVs) that contain parasite-derived RNA. However, the significance of the secreted RNA remains unexplored. Here, we compare secreted and intracellular RNA from asexual cultures of six P. falciparum lines. We find that secretion of RNA via extracellular vesicles is not only periodic throughout the asexual intraerythrocytic developmental cycle but is also highly conserved across P. falciparum isolates. We further demonstrate that the phases of RNA secreted via extracellular vesicles are discernibly shifted compared to those of the intracellular RNA within the secreting whole parasite. Finally, transcripts of genes with no known function during the asexual intraerythrocytic developmental cycle are enriched in PfEVs compared to the whole parasite. We conclude that the secretion of extracellular vesicles could be a putative posttranscriptional RNA regulation mechanism that is part of or synergise the classic RNA decay processes to maintain intracellular RNA levels in P. falciparum.

It is increasingly clear that machine learning algorithms need to be integrated in an iterative scientific discovery loop, in which data is queried repeatedly by means of inductive queries and where the computer provides guidance to the experiments that are being performed. In this chapter, we summarise several key challenges in achieving this integration of machine learning and data mining algorithms in methods for the discovery of Quantitative Structure Activity Relationships (QSARs). We introduce the concept of a robot scientist, in which all steps of the discovery process are automated; we discuss the representation of molecular data such that knowledge discovery tools can analyse it, and we discuss the adaptation of machine learning and data mining algorithms to guide QSAR experiments.