Therapeutic target discovery using Boolean network attractors: improvements of kali

In a previous article, an algorithm for identifying therapeutic targets in Boolean networks modeling pathological mechanisms was introduced. In the present article, the improvements made on this algorithm, named kali, are described. These improvements are i) the possibility to work on asynchronous Boolean networks, ii) a finer assessment of therapeutic targets and iii) the possibility to use multivalued logic. kali assumes that the attractors of a dynamical system, such as a Boolean network, are associated with the phenotypes of the modeled biological system. Given a logic-based model of pathological mechanisms, kali searches for therapeutic targets able to reduce the reachability of the attractors associated with pathological phenotypes, thus reducing their likeliness. kali is illustrated on an example network and used on a biological case study. The case study is a published logic-based model of bladder tumorigenesis from which kali returns consistent results. However, like any computational tool, kali can predict but can not replace human expertise: it is a supporting tool for coping with the complexity of biological systems in the field of drug discovery

PENERAPAN PENDEKATAN SAVI (SOMATIS AUDITORI VISUAL INTELEKTUAL)UNTUK MENINGKATKAN KREATIVITAS DALAM PEMBELAJARAN MATEMATIKA VOLUME BANGUN RUANG

Abstract: The aim of this reserach is To promote creativity in learning mathematics geometrical materials in class V SD Negeri 02 Bolong SAVI approach (Visual Auditory Intellectual somatic). This research belongs to a classroom action research. The research was carried out in two cycles. Each cycle consists of planning, action, observation, and reflection. Data sources consist of primary data source, namely, data obtained from students, teacher, headmaster, and parent of student and, secondary data source includes archives/documents, test of learning performance, and observation sheet. The data is collected by using observation, interview and documentation.Data validity is examined by using content validity, data triangulation and methodological triangulation. Data analysis of the research uses interactive model consisting of three components, namely, data reduction, data presentation, and conclusion drawing or verification. Inconclusion the application of the approach SAVI (Visual Auditory Somatic Intelektual) can improve creativity students in learning mathematics geometrical volume of material. Abstrak: Tujuan penelitian ini adalah untuk meningkatkan kreativitas dalam pembelajaran matematika materi bangun ruang pada siswa kelas V SD Negeri 02 Bolong melalui pendekatan SAVI (Somatis Auditori Visual Intelektual).Penelitian dilaksanakan dalam dua siklus. Setiap siklus terdiri dari perencanaan, pelaksanaan tindakan, observasi, dan refleksi.Sumber data berupa sumber data pokok (Primer) yaitu dari para siswa, guru, kepala sekolah dan orang tua siswa dan sumber data sekunder meliputi arsip/dokumen, tes hasil belajar, dan lembar observasi.Teknik Pengumpulan data menggunakan observasi,wawancara, dan dokumentasi.Validitas data menggunakan validitas isi, teknik trianggulasi data dan triangulasi metode. Teknik analisis data menggunakan teknik analisis model interaktif yang terdiri dari tiga komponen analisis yaitu reduksi data, sajian data dan penarikan kesimpulan atau verifikasi.Simpulan bahwapenerapan pendekatan SAVI (Somatis Auditori Visual Intelekrual) dapat meningkatkan krativitas siswa dalam pembelajaran matematika materi volume bangun ruang. Kata kunci: SAVI (Somatis, Auditori, Visual, Intelektual),kreativitas dalam pembelajaran Matematik

Olive polyphenol effects in a mouse model of chronic ethanol addiction

Objectives Alcohol addiction elicits oxidative imbalance and it is well known that polyphenols possess antioxidant properties. We investigated whether or not polyphenols could confer a protective potential against alcohol-induced oxidative stress. Methods We administered (per os) for two months 20 mg/kg of olive polyphenols containing mostly hydroxytyrosol in alcoholic adult male mice. Hydroxytyrosol metabolites as hydroxytyrosol sulfate 1 and hydroxytyrosol sulfate 2 were found in the serum of mice administered with polyphenols with the highest amount in animals treated with both polyphenols and alcohol. Oxidative stress was evaluated by FORT (free oxygen radical test) and FORD (free oxygen radical defense) tests. Results Alcoholic mice showed a worse oxidative status than nonalcoholic mice (higher FORT and lower FORD) but polyphenol supplementation partially counteracted the alcohol pro-oxidant effects, as evidenced by FORT. Conclusions A better understanding of the antioxidant protection provided by polyphenols might be of primary interest for drug discovery and dietary-based prevention of the damage associated with chronic alcohol abus

Integrating Time-Series Data in Large-Scale Discrete Cell-Based Models

International audienceIn this work we propose an automatic way of generating and verifying formal hybrid models of signaling and transcriptional events, gathered in large-scale regulatory networks.This is done by integrating temporal and stochastic aspects of the expression of some biological components. The hybrid approach lies in the fact that measurements take into account both times of lengthening phases and discrete switches between them. The model proposed is based on a real case study of keratinocytes differentiation, in which gene time-series data was generated upon Calcium stimulation. To achieve this we rely on the Process Hitting (PH) formalism that was designed to consider large-scale system analysis. We first propose an automatic way of detecting and translating biological motifs from the Pathway Interaction Database to the PH formalism. Then, we propose a way of estimating temporal and stochas-tic parameters from time-series expression data of action on the PH. Simulations emphasize the interest of synchronizing concurrent events

Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth.

Migration stimulating factor (MSF) is a genetically truncated N-terminal isoform of fibronectin that is highly expressed during mammalian development in fetal fibroblasts, and during tumor formation in human cancer-associated myofibroblasts. However, its potential functional role in regulating tumor metabolism remains unexplored. Here, we generated an immortalized fibroblast cell line that recombinantly overexpresses MSF and studied their properties relative to vector-alone control fibroblasts. Our results indicate that overexpression of MSF is sufficient to confer myofibroblastic differentiation, likely via increased TGF-b signaling. In addition, MSF activates the inflammation-associated transcription factor NFκB, resulting in the onset of autophagy/mitophagy, thereby driving glycolytic metabolism (L-lactate production) in the tumor microenvironment. Consistent with the idea that glycolytic fibroblasts fuel tumor growth (via L-lactate, a high-energy mitochondrial fuel), MSF fibroblasts significantly increased tumor growth, by up to 4-fold. Mechanistic dissection of the MSF signaling pathway indicated that Cdc42 lies downstream of MSF and fibroblast activation. In accordance with this notion, Cdc42 overexpression in immortalized fibroblasts was sufficient to drive myofibroblast differentiation, to provoke a shift towards glycolytic metabolism and to promote tumor growth by up to 2-fold. In conclusion, the MSF/Cdc42/NFκB signaling cascade may be a critical druggable target in preventing Warburg-like cancer metabolism in tumor-associated fibroblasts. Thus, MSF functions in the metabolic remodeling of the tumor microenvironment by metabolically reprogramming cancer-associated fibroblasts toward glycolytic metabolism

Ganancia de peso excesiva durante la gestación como factor de riesgo de preeclampsia

Objetivo: Demostrar si la ganancia de peso excesiva gestacional es factor de riesgo de preeclampsia en gestantes a término. Materiales y métodos: Desarrollamos un análisis de casos y controles de tipo retrospectivo, con historias clínicas, en una muestra de 3673 gestantes atendidas en el servicio de gineco-obstetricia del Hospital Regional Docente de Trujillo (HRDT) del 2012 al 2017, que cumplieron con los criterios de selección. La asociación de los factores de estudio fue determinada por el test de Chi – cuadrado y cuantificado por el Odds Ratio (OR) <0.05 Resultados: La prevalencia de preeclampsia fue de 10.24 %, de los cuales, 376 pacientes correspondían a los casos, donde, 117 presentaron preeclampsia leve y 259 preeclampsia severa. En el grupo control, el peso promedio pre gestacional fue mayor, pero la ganancia excesiva de peso gestacional (GEP) fue mayor en el grupo de pacientes con preeclampsia; 28.99 % de los casos presentaron GEP y de los controles el 23.81%. Con un OR de 1.306 con IC al 95% de 1.03 – 1.66, p = 0.027, se indica que es un factor de riesgo para la preeclampsia- Conclusión: La ganancia excesiva de peso durante la gestación es factor asociado a preeclampsiaObjective: To demonstrate whether the gain of excessive gestational weight is a risk factor for pre-eclampsia in full-term pregnant women. Materials and methods: We developed a case-control analysis of retrospective population, with clinical records, in a sample of 3673 pregnant women attended the obstetrics and gynecology service of the HRDT from 2012 to 2017 that met the selection criteria. The association of the study factors was determined by the Chi - square test X ^ 2 and quantified by the Odds Ratio (OR) <0.05 Results: The prevalence of preeclampsia was 10.24%, of which 376 patients corresponded to cases, where 117 had mild preeclampsia and 259 severe preeclampsia. The 28.99% of the cases presented excessive weight gain and the controls 23.81%. The average pre-pregnancy weight was higher in the control group, but the excess of gestational weight was higher in the group of patients with preeclampsia. With an OR of 1306 with 95% CI of 1.03 - 1.66, p = 0.027, indicating that excessive weight gain (GEW) is a risk factor for preeclampsia Conclusion: Excessive weight gain during pregnancy is a factor associated with preeclampsiaTesi

Exploring the determinant of environmental performance in higher education

This paper aims to examine the role of green responsible leadership and green human resource management on environmental performance. In this paper, it is also aimed to examine green orchestration innovation as a mediator. We employed a SmartPLS 4.0 using the SEM-PLS method. A dataset of 150 respondents from students who are active in the top 3 green campuses in East Java, Indonesia was collected using a questionnaire. Main findings of the study demonstrate that (i) green responsible leadership have a significant effect on environmental performance, (ii) green human resource management have a significant effect on environmental performance, and finally (iii) green orchestration innovation acts as a mediator between green responsible leadership and green human resource management on environmental performance. Universities must optimize their resources by orchestrating them through innovation. Furthermore, universities must establish clear regulations to support environmental protection, starting with the learning process, policies, curriculum, and daily activities that can become a model for students' lives after graduation

PENERAPAN PENDEKATAN SAVI ( SOMATIS AUDITORI VISUAL INTELEKTUAL ) UNTUK MENINGKATKAN KREATIVITAS DALAM PEMBELAJARAN MATEMATIKA MATERI VOLUME BANGUN RUANG PADA SISWA KELAS V SD NEGERI 02 BOLONG KABUPATEN KARANGANYAR TAHUN AJARAN 2012/2013

The aim of this research is increase creativity matematics learning in the wake of the volume to the 5 thgrade student of SD Negeri 02 Bolong karanganayr regency with SAVI (Somatic Auditory Visual Intelectual) aplication approach. The form of this research is class action research role in two cycles. Each cycle consists of four stages, planning, action, observation and reflection. The subjects were students of class V SD Negeri 02 Bolong totaling 16 students. Data collection techniques used are documentation, interviews and observations. The data analysis technique used is interactive analysis model consists of four stages, namely data collection, data reduction, data presentation, and conclusion. Test the validity of the data used in this research is content validity, triangulation of data and triangulation methods. Based on these results it can be concluded that the application of the approach SAVI (Somatic Auditory Visual Intelectual) can increase students creativity in learning mathematics geometrical volume of material. Such improvements can be evidenced by the increasing value of the creativity of students in mathematics learning materials geometrical volume cubes and blocks in each cycle. Before action (initial conditions) the average value of the creativity of students in learning mathematics with only 1.23 percent of students who achieve the classical completeness value creativity more or equal to the category of medium (1.6 to 2.4) by 25% (4 students). In I cycle the average value of the creativity of students in learning mathematics at 1.73 with classical completeness percentage of students who achieve value creativity more or the same category (1.6 to 2.4) by 63% (10 students). And the second cycle of the average value of the creativity of students in learning mathematics at 2.24 with classical completeness percentage of students who achieved greater than or equal value of creativity by category (1.6 to 2.4) by 81% (13 students). Tujuan Penelitian ini adalah: Untuk meningkatkan kreativitas dalam pembelajaran matematika materi bangun ruang pada siswa kelas V SD Negeri 02 Bolong Kabupaten Karanganyar melalui pendekatan SAVI (Somatis Auditori Visual Intelektual). Bentukpenelitian ini adalah penelitian tindakan kelas yang dilaksanakan dalan dua siklus. Tiap siklus terdiri dari 4 tahapan yaitu perencanaan, pelaksanaan tindakan, observasi dan refleksi. Subjek penelitian ini adalah siswa kelas V SD Negeri 02 Bolong yang berjumlah16 siswa.Teknik pengumpulan data yang digunakan adalah dokumentasi, wawancaradanobservasi.Teknik analisis data yang digunakan adalah model analisis interaktif yang terdiri dari empat tahapan yaitu pengumpulan data, reduksi data, penyajian data, dan penarikan kesimpulan. Uji validitas data yang digunakan dalam penelitian ini adalah validitas isi, triangulasi data dan triangulasi metode. Berdasarkan hasil penelitian dapat disimpulkan bahwa penerapan pendekatan SAVI (Somatis Auditori Visual Intelekrual) dapat meningkatkan krativitas siswa dalam pembelajaran matematika materi volume bangun ruang. Peningkatan tersebut dapat dibuktikan dengan meningkatnya nilai kreativitas siswa dalam pembelajaran matematika materi volume bangun ruang kubus dan balok pada setiap siklusnya. Sebelum tindakan (kondisi awal) nilai rata-rata kreativitas siswa dalam pembelajaran matematika hanya 1,23 dengan persentase ketuntasan klasikal siswa yang mencapai nilai kreativitas lebih atau sama dengan kategori sedang (1,6 2,4) sebesar25% (4 siswa). Pada siklus I nilai rata-rata kreativitas siswa dalam pembelajaran matematika sebesar 1,73 dengan persentase ketuntasan klasikal siswa yang mencapai nilai kreativitas lebih atau sama dengan kategori sedang (1,6 2,4) sebesar 63% (10 siswa). Dan siklus II nilai rata-rata kreativitas siswa dalam pembelajaran matematika sebesar 2,24 dengan persentase ketuntasan klasikal siswa yang mencapai nilai kreativitas lebih atau sama dengan kategori sedang (1,6 2,4) sebesar 81% (13 siswa)

MANAJEMEN ALOKASI DANA DESA DI DESA SUMBER AGUNG KECAMATAN MEPANGA KABUPATEN PARIGI MOUTONG

This research intends to identify the management process of villagen fund allocation in Sumber Agung Villagen Mepanga Sub-district Parigi Moutong Regency. This is a case study research using qualitative approach. The location and key informant were determined using purposive sampling. Data collected were analyzed is phases based on data information from informant through observation, document, and interview. Based on research conducted it can be concluded that the application of management functions of village fund allocation in Sumber Agung Village Mepanga Sub-district Parigi Moutong Regency have not fully optimum yet. It can be seen through planning administration that has not rum well because it does not match to planning the implementation of programs and activities. Organization doing by the government in Sumber Agung village has not run based on its function and principle due to the inadequate of humann resource completence. Those problrms become main factor in affecting the implementation of management of village fund allocation. Supervising conducted by the head of village continually of periodically to this village fund has not optimally implementd

Signed permutations and the signed permutahedron

The permutahedron Δn is a polytope in Rn whose vertices are in bijection with the elements of the symmetric group Sn. Vertices of the permutahedron are adjacent if their corresponding elements of Sn differ by an adjacent transposition. The symmetric group Sn is one among a family of groups Gpr, nq which are themselves a special case of complex reflection groups. The group Gpr, nq is the group of nˆn matrices such that there is exactly one nonzero entry in each row and column, and this entry is an rth root of unity. In this thesis, we explore the question of whether there is a polytope whose face structure is related to Gpr, nq in the same way that the permutahedron is related to Sn – Gp1,nq. We will answer that question for the case where r " 2. We construct a polytope Δ2,n and show the vertices are in bijection with the elements of Gp2,nq. We then prove that the adjacency of vertices in Δ2,n is encoded by a subset of Gpr, nq which is analogous to the adjacent transpositions.https://doi.org/10.46569/20.500.12680/kw52jf42