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Introduction: Multiple myeloma (MM) is an incurable bone marrow (BM)-based cancer involving clonal plasma cells. Most patients show elevated levels of serum monoclonal protein (sMP) and kappa or lambda serum free light chains (sFLCs) at diagnosis. However, around 1–2% of patients, termed nonsecretory, do not produce these biomarkers. As the disease progresses, more patients may become unevaluable using conventional markers, requiring invasive and expensive procedures like BM biopsies and positron emission tomography-computed tomography (PET-CT) scans for assessment and highlighting the need for alternative methods to monitor disease progression. Case Presentation: We present a case report of an MM patient who developed nonsecretory disease during his second line of treatment when he complained of new rib pain; progressive disease was then confirmed on a PET-CT scan. The patient showed an increase in his serum B-cell maturation antigen (sBCMA) levels whereas his conventional myeloma markers did not detect disease activity (sMP remained undetectable and involved sFLC level was normal). After starting a new treatment regimen, his rib pain disappeared, PET-CT scan improved, and sBCMA levels decreased. Upon relapse, he developed increased rib pain with a rising sBCMA level; his conventional myeloma markers did not detect disease activity. After changing to a new regimen, his rib pain improved, and this was accompanied by a decrease in his sBCMA levels. Conclusion: Thus, this case exemplifies the potential for sBCMA to provide a non-invasive method for monitoring MM patients who develop nonsecretory disease.

Despite major therapeutic advancements in recent years, multiple myeloma (MM) remains an incurable disease with nearly all patients experiencing relapsed and refractory disease over the course of treatment. Extending the duration and durability of clinical responses will necessitate the development of therapeutics with novel targets that are capable of robustly and specifically eliminating myeloma cells. B-cell maturation antigen (BCMA) is a membrane-bound protein expressed predominantly on malignant plasma cells and has recently been the target of several novel therapeutics to treat MM patients. This review will focus on recently approved and currently in development agents that target this protein, including bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T-cell therapies. In addition, this protein also serves as a novel serum biomarker to predict outcomes and monitor disease status for MM patients; the studies demonstrating this use of BCMA will be discussed in detail.

Brand exposure monitoring adalah bentuk khusus dari media monitoring yang bertujuan memantau paparan merek dan brand mention pada media-media publisitas. Penelitian ini mengusulkan model kerangka kerja pemonitoran brand exposure (paparan merek) melalui analisis pada media-media publisitas memanfaatkan formulasi kueri dan pemodelan topik, bertujuan mengekstraksi topik-topik utama yang terkandung dalam media eksternal atau media massa, dan membandingkannya dengan media internal institusi. Ekstraksi topik dilakukan menggunakan metode Latent Dirichlet Allocation (LDA) pada data teks berupa SERP (Search Engine Results Page) snippets. Pemrosesan berikutnya memanfaatkan penghitungan Jaccard index dan cosine similarity. Output dari kerangka kerja berupa visualisasi topik yang merepresentasikan tema dari artikel-artikel yang memaparkan brand institusi, dan metrik pengukuran yang berguna untuk analisis pengambilan keputusan terkait pengelolaan media dan komunikasi institusi. Pengujian rancangan kerangka kerja menggunakan sampel data menghasilkan output sesuai ekspektasi, yaitu kelompok topik yang terbentuk dapat mewakili topik-topik dominan dalam kedua kategori media pada periode pemonitoran, dengan tingkat coverage tertinggi mencapai 82,69% dan similaritas 33,97%. Penggunaan metode LDA dalam penelitian ini memiliki keterbatasan, yaitu terbentuknya kelompok topik yang tidak murni berisi topik tunggal, melainkan terdiri dari beberapa subtopik. Namun demikian, hal ini tidak mengurangi kebermanfaatan kerangka kerja.

Program Merdeka Belajar Kampus Merdeka (MBKM) menyediakan fasilitas bagi mahasiswa untuk mengalihkan kredit dari aktivitas kerja ke mata kuliah tertentu. Untuk mendukung proses ini, penelitian ini menggunakan teknologi Semantik Web dengan mengintegrasikan ontologi yang dibangun menggunakan alat Protégé. Melalui penggunaan bahasa query SPARQL, teknologi Semantik Web memungkinkan pencarian yang efisien dan akurat antara deskripsi aktivitas dan mata kuliah berdasarkan konteks dan arti semantik data. Hasil penelitian menunjukkan penelitian ini dapat mengambil informasi yang diperlukan secara efisien dan akurat dari ontologi yang telah dikembangkan.

The sales department of a distribution company is one of the places where fraud often occurs. This fraud occurs in various ways and causes massive losses for the company. These frauds have certain patterns. The patterns that occur in these practices are studied by the company's internal auditor experts. The experience of these experts is processed into a system called the Expert System. The support of a technology-based tool is needed in order to detect sales fraud early. The purpose of this research is to be able to provide benefits for companies with early detection of fraud in the sales department. At the time this research was conducted, researchers had not found similar research with the same object. In this research, a comparison of various machine learning algorithm models will be carried out with the aim of knowing whether using machine learning technology can help detect fraud with a high accuracy value. The algorithm method used is supervised learning method. The algorithm models to be compared are Decision Tree, K-Nearest Neighbor, Random Forest, SVM and Logistic Regression. It is expected that by using machine learning technology, fraud can be detected early, so that the level of loss and risk of sales can be minimized.

Banyaknya pilihan jurusan studi yang ditawarkan oleh perguruan tinggi dapat memberikan kesempatan memilih yang lebih luas kepada calon mahasiswa. Namun di sisi lain, juga dapat menimbulkan kesulitan bagi siswa untuk menentukan pilihan yang tepat. Pemilihan jurusan studi perguruan tinggi dipengaruhi oleh beberapa faktor, di antaranya adalah faktor peminatan siswa, jurusan yang dipilih pada jenjang sekolah sebelumnya, cita-cita siswa, juga faktor persyaratan masuk di perguruan tinggi tertentu. Penelitian ini bertujuan membuat model sistem informasi yang dapat mempermudah seorang siswa memperoleh informasi mengenai jurusan studi yang paling tepat, di antara banyaknya program studi yang ditawarkan. Informasi yang dihasilkan oleh sistem ini dapat menjadi referensi pendukung rekomendasi bagi calon mahasiswa untuk menentukan program studi yang akan ia pilih. Sistem dirancang dengan memanfaatkan teknologi web semantik, dengan membangun ontologi berdasarkan beberapa knowledge base yang dihubungkan sebagai representasi pengetahuan baru. Rancangan model ontologi dalam format OWL berhasil menghubungkan beberapa knowledge base menjadi pengetahuan yang komprehensif dan kontekstual sebagai sumber informasi pendukung yang dapat digunakan oleh seorang calon mahasiswa memilih program studi berdasarkan rekomendasi tersebut. Pemodelan ontologi dilakukan menggunakan perangkat lunak Protege, dan implementasi pada web server dilakukan menggunakan platform Apache Jena.

Abstract Background Multiple myeloma (MM) patients have variable responses to mRNA vaccination to COVID‐19. Little is known regarding their vaccine‐induced antibody levels over time. Methods We monitored spike IgG antibody levels over 24 weeks among a subset of 18 MM patients who showed a full response after two mRNA vaccinations. Results MM patients had a more rapid decline in antibody levels as compared to eight healthy controls, with power law half‐lives of 72 days (vs. 107 days) and exponential half‐lives of 37 days (vs. 51 days). The patients with longer SARS‐CoV‐2 antibody half‐lives were more likely to have undetectable monoclonal protein than those with shorter half‐lives, suggesting better disease control may correlate with longer duration of vaccine‐induced antibodies. Regardless, by 16 weeks post‐second dose of mRNA vaccination, the majority of patients had antibody levels below 250 binding arbitrary units per milliliter, which would be unlikely to contribute to preventing COVID‐19. Conclusions Thus, even MM patients who respond adequately to vaccination are likely to require more frequent booster doses than the general population.

Using digital signature in a document, especially in work from home situation, becomes crucial to misuse. The digital signature is a schema to identify somebody uniquely and to prove the originality of a document. The development of information technology allows digital signatures as a tool to ensure the originality of information. The aim of the study is to develop an application that uses Quick Response (QR) Code as a digital signature. So QR Code can work as a tool to authenticate the leader’s signature or document verification. After the application was built and applied, users’ evaluation was performed through questionnaires. The result shows that 44% of users state that the application has been well used and beneficial. There are some suggestions for application revision from 34% of users, whereas 22% have no comment.

Abstract Launched in 2019, the French Citizens’ Convention for Climate (CCC) tasked 150 randomly chosen citizens with proposing fair and effective measures to fight climate change. This was to be fulfilled through an “innovative co-construction procedure”, involving some unspecified external input alongside that from the citizens. Did inputs from the steering bodies undermine the citizens’ accountability for the output? Did co-construction help the output resonate with the general public, as is expected from a citizens’ assembly? To answer these questions, we build on our unique experience in observing the CCC proceedings and documenting them with qualitative and quantitative data. We find that the steering bodies’ input, albeit significant, did not impair the citizens’ agency, creativity, and freedom of choice. While succeeding in creating consensus among the citizens who were involved, this co-constructive approach, however, failed to generate significant support among the broader public. These results call for a strengthening of the commitment structure that determines how follow-up on the proposals from a citizens’ assembly should be conducted.

Europe, perhaps more than any other region in the world, is characterized by the presence of border cities and conurbations, urban areas whose morphological and functional continuity can be felt across one or several national borders. In 2010, the ESPON Metroborder program thus identified some forty urban communities within the EU and on its limits. However, this dimension of towns and borders has long been neglected, by the states as much as by the European Union. And yet, as part of the opening regime specific to internal borders, those urban spaces are emblems and vectors of European integration on the local scale. This article demonstrates how border cities have been an essential part of the European integration process since its very beginning and how their contribution has been fostered by the EU’s regional policy programs, especially since the 2000s, helping them to be recognized as specifically dynamic urban border spaces and to use this label in order to develop a multitude of cross-border projects.

BackgroundThere is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka.ObjectivesTo assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA).MethodsWe selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo.ResultsThe median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up.ConclusionsThe 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.

IntroductionHuanglonbing (HLB) is the most serious disease of citrus in the world, associated with three non-cultivable phloem-restricted bacteria Candidatus Liberibacter asiaticus (CLas), Ca L. africanus (CLaf) and Ca L. americanus (CLam). CLas is transmitted by the Asian citrus psyllid Diaphorina citri, and has spread to several countries. The African psyllid Trioza erytreae, the vector of CLaf occurs in Africa and neighbouring islands. Only two major citrus-growing regions - Australia/New Zealand and the Mediterranean Basin - are still HLB-free in the world. However, T. erytreae has recently been introduced into continental Europe (Portugal and Spain) and has become a potential threat to citrus production. The transmission of CLas by T. erytreae had been postulated but never tested. To evaluate the risk of T. erytreae transmitting CLas, comparative transmissions of CLas by T. erytreae and D. citri were assessed.MethodsTransmission tests were performed on excised leaves and seedlings of Citrus volkameriana with different inoculation access periods (in series) for both insect species. Quantifications of bacterial titers were made in excised leaves, seedlings three and six months after inoculation and on individual insects.ResultsOur results showed that T. erytreae was able to efficiently acquire CLas. Furthermore, T. erytreae carried significantly higher bacterial titers than D. citri, and was able to efficiently transmit the bacteria to seedlings at a similar rate that D. citri highlighting the high risk of spread of the most aggressive variant of HLB (CLas) by T. erytreae in Europe.DiscussionThus, extreme precautions to prevent any entry of CLas into Europe should be adopted.

Background: Since the beginning of the pandemic, COVID-19 has been regarded as an exceptional disease. Control measures have exclusively focused on ‘the virus’, while failing to account for other biological and social factors that determine severe forms of the disease. Aim: We argue that although COVID-19 was initially considered a new challenge, justifying extraordinary response measures, this situation has changed — and so should our response. Main arguments: We now know that COVID-19 shares many features of common infectious respiratory diseases, and can now ascertain that SARS-CoV-2 has not suddenly presented new problems. Instead, it has exposed and exacerbated existing problems in health systems and the underlying health of the population. COVID-19 is evidently not an ‘extraterrestrial’ disease. It is a complex zoonotic disease, and it needs to be managed as such, following long-proven principles of medicine and public health. Conclusion: A complex disease cannot be solved through a simple, magic-bullet cure or vaccine. The heterogeneity of population profiles susceptible to developing a severe form of COVID-19 suggests the need to adopt varying, targeted measures that are able to address risk profiles in an appropriate way. The critical role of comorbidities in disease severity calls for short-term, virus-targeted interventions to be complemented with medium-term policies aimed at reducing the burden of comorbidities, as well as mitigating the risk of transition from infection to disease. Strategies required include upstream prevention, early treatment, and consolidation of the health system.

Background: Patients with multiple myeloma have unpredictable responses to vaccination for COVID-19. Anti-spike antibody levels can determine which patients develop antibodies at levels similar to healthy controls, and are a known correlate of protection. Case report: A multiple myeloma patient developed protective anti-spike antibodies after vaccination (608 IU/mL), but nonetheless developed severe breakthrough COVID-19 just 10 weeks following his second vaccination with mRNA-1273. Results: Sequencing of the viral isolate revealed an extensively mutated variant with 10 spike protein mutations, including E484Q and N440K. Serology testing showed a dramatic decline in anti-spike antibodies immediately prior to virus exposure. Conclusions: Multiple myeloma patients who do develop detectable antibody responses to vaccination may be at increased risk for breakthrough infections due to rapid decline in antibody levels. Viral variants with immune escape mutations such as N440K, also seen independently in the SARS-CoV-2 Omicron variant (B.1.1.529) and in viral passaging experiments, likely require a higher level of anti-spike antibodies to prevent severe COVID-19.

Teaching and learning activities need to be interactive to increase children’s interest in learning. With the utilization of technology, there are so many learning tools had been made. One of them is Moodle. Moodle is a learning management system (LMS) application to support learning activity on electronic based (e-learning). The purpose of this research is to implement Moodle as LMS for mathematics learning on primary school children. By using Moodle, the lessons are delivered interactively for children to learn. This research will find out the influence of using this application towards the test score before and after using the application. T-Test analysis will be applied to analyze the differences. Besides analyzing the test score, questionnaires for the children who test the application will be given to know the effect of using the application for them. Based on the evaluation result using T-Test analysis, there were not any significant differences, but there were enhancements in average, highest, and lowest scores, along with the decrease in standard deviation. The result of correlation coefficient calculation between exercise frequency and quiz result was 0.2162, which meant that the correlation was weak or almost no correlation. Based on the questionnaire result, this application is considered helping children in understanding the subject.

We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer’s disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), moderate hAChE (IC50 = 1.73 ± 0.34 μM), hMAO A (IC50 = 2.78 ± 0.12 μM), and MAO B (IC50 = 21.29 ± 3.85 μM) inhibition, while keeping a strong antioxidant power (3.04 TE, ORAC test). Consequently, the results reported here support the development of new multitarget Donepezil + Chromone + Melatonin hybrids, such as compound 14n, as a potential drug for AD patients cure.

In view of the multifactorial nature of Alzheimer’s disease (AD), multitarget small molecules (MTSM) represent the most potent and attractive therapeutic strategy to design new drugs for Alzheimer’s disease therapy. The new MTSM KojoTacrines (KTs) were designed and synthesized by juxtaposition of selected pharmacophoric motifs from kojic acid and tacrine. Among them, 11-amino-2-(hydroxymethyl)-12-(3-methoxyphenyl)-7,9,10,12-tetrahydropyrano [2',3':5,6] pyrano[2,3-b]quinolin-4(8H)-one (KT2d) was identified as less-hepatotoxic than tacrine, at higher concentration, a moderate, but selective human acetylcholinesterase inhibitor (IC50 = 4.52 ± 0.24 µM), as well as an antioxidant agent (TE = 4.79) showing significant neuroprotection against Aβ1–40 at 3 µM and 10 µM concentrations. Consequently, KT2d is a potential new hit-ligand for AD therapy for further biological exploration.

Agile is a system development life cycle methodology that focuses on development interactions that involve the user with the development team led by the project manager as an intermediary between the client and the development team, with the project manager as the project leader, it is expected that this role can carry out project planning by making estimates and designing. project. The worst thing that can happen if the application fails to meet client expectations is the additional development time called maintenance, this risk will create losses to the company even though maintenance is an additional service, but this risk tends to be negative because it can have a negative impact on the company and members of the development team. responsible for the project, the project manager must be able to identify risks earlier during the sprint, so in this study we will discuss the analysis and risk identification of maintenance programs in agile-based project management, as a research analyst method will use a classification tree to group them so that It can be found at the sprint stage how much risk has started to be made, so that the project manager can make corrections at the next sprint to reduce maintenance risk

Abstract — Social Media Network has been an important information source, and the information propagation within the network gave an impact on politics, marketing, and entertainment industry. Our aim is to predict a tweet whether the information will be propagated further. The previous research has focused on analyzing this task with a wide range of learning methods and features, such as content and account features. Timeline features are proposed as features that can further predict information propagation and as we compared the performance with content and account features. The dataset consists of 43.229 tweets, we predict the information propagation with logistic regression, support vector machines, and random forest learning method with these features. Our result indicates that the timeline feature can be a good candidate for predicting information propagation and the random forests learning method consistently performs better. From the training result, we further calculate feature importance. Recently tweets, engagement with another user and previous liked tweets on the timeline features contributed to more popular tweets.

Current development of the internet world has been growing rapidly, especially in the field of website. People use search engines to find the news or information they needed on a website. One of the many indications of the success of a website is traffic. Traffic could be received from various factors, one of which is website rank in Search Engine Result Page (SERP). To improve the SERP, SEO methods are required. This research will implement SEO to website especially on the image, and then analyzed by using a tester tools, for example SEOptimer, Pingdom Tools, and SEO Site Checkup. After the website has been optimized, tested with the same tester tools. From the research results can be seen whether image optimization can affect SERP.

Currently, Indonesian government is changing the government system into an Sistem Pemerintahan Berbasis Elektronik (SPBE) or often heard as e-government. With this change in the government system, it has an impact on various sector of life. One of many sectors is construction service sector. LPJK as a non-structural institution under Ministry of Public Works and Public Housing issued a letter to the construction services association regarding the development of integrated application with SIKI LPJK. LPJK and OSS institutions has implemented digital signatures on business entity licensing document. Construction service associations has responded to develop of these regulations by creating an association information system application that implements digital signatures. This research was conducted to apply an digital signatures to the validation of the Membership Card using the secure hash algorithm (SHA) and advanced encryption standard (AES) methods generated through the association information system. This application generates an digital signatures which is implemented with QR Code. The existence of this application is expected to be a form of support for the government which is making changes to the government system.

The Faculty of Information Technology is one of the faculties at Maranatha Christian University Bandung. One of the study programs in the Faculty of Information Technology is Informatics Engineering Department. Nowadays, the management of Final Project and Final Project Seminar is still managed manually. In this research, we did this research to digitalize any documents and scoring grades by using this system for student’s final project. This causes the data management process related to the process of recording and completing the final project relying only on Microsoft Excel. In this research, an analysis and application design carried out to assist the process of recording the journey of students in completing the Final Project Assignment. The result from this research is an application prototype that can be used by course coordinators to manage grades of final project and final project seminar. This application is a web-based, built using PHP with Firebase database.

Background Transcatheter aortic valve replacement (TAVR) requires large‐bore access, which is associated with bleeding and vascular complications. ProGlide and Prostar XL are vascular closure devices widely used in clinical practice, but their comparative efficacy and safety in TAVR is a subject of debate, owing to conflicting results among published studies. We aimed to compare outcomes with Proglide versus Prostar XL vascular closure devices after TAVR. Methods and Results This large‐scale analysis was conducted using RISPEVA, a multicenter national prospective database of patients undergoing transfemoral TAVR treated with ProGlide versus Prostar XL vascular closure devices. Both multivariate and propensity score adjustments were performed. A total of 2583 patients were selected. Among them, 1361 received ProGlide and 1222 Prostar XL. The predefined primary end point was a composite of cardiovascular mortality, bleeding, and vascular complications assessed at 30 days and 1‐year follow‐up. At 30 days, there was a significantly greater reduction of the primary end point with ProGlide versus Prostar XL (13.8% versus 20.5%, respectively; multivariate adjusted odds ratio, 0.80 [95% CI, 0.65–0.99]; P=0.043), driven by a reduction of bleeding complications (9.1% versus 11.7%, respectively; multivariate adjusted odds ratio, 0.76 [95% CI, 0.58–0.98]; P=0.046). Propensity score analysis confirmed the significant reduction of major adverse cardiovascular events and bleeding risk with ProGlide. No significant differences in the primary end point were found between the 2 vascular closure devices at 1 year of follow‐up (multivariate adjusted hazard ratio, 0.88 [95% CI, 0.72–1.10]; P=0.902). Comparable results were obtained by propensity score analysis. During the procedure, compared with Prostar XL, ProGlide yielded significant higher device success (99.2% versus 97.5%, respectively; P=0.001). Conclusions ProGlide has superior efficacy as compared with Prostar XL in TAVR procedures and is associated with a greater reduction of composite adverse events at short‐term, driven by lower bleeding complications. Registration Information URL: clini​caltr​ials.gov; Unique identifier: NCT02713932.

The previous genetic characterization of the honeybee population of Mauritius Island (Indian Ocean) revealed an ongoing process of hybridization between the first established African subspecies Apis mellifera unicolor and recently imported European subspecies (A. m. ligustica, A. m. carnica and A. m. mellifera). This context offers the rare opportunity to explore the influence of hybridization between African and European honeybees on phenotypic traits out of the case largely studied of the Africanized honeybee (hybrid between A. m. scutellata from South Africa and European subspecies). We thus conducted geometric morphometric analyses on forewings of 283 workers genetically characterized at 14 microsatellite loci to evaluate (1) if the morphological variability coincides well with the neutral genetic variability, (2) if hybrids exhibited rather parental, intermediate or transgressive traits, and (3) to test if fluctuating asymmetry (FA) of size and shape, as a measure of developmental stability, was elevated in hybrids (due to genetic stress) and/or European bees (due to unsuitable environment) compared to African bees. A strong concordance was found between morphological variability and neutral genetic variability, especially for wing shape, based on partial least-square analyses (PLS). However, on average, the morphology of hybrids was more similar to the African bees, potentially reflecting the dynamics and direction of introgression. Significant FA for wing size as well as wing shape was detected, suggesting the overall presence of stress during the development of the studied individuals. In contrast, the asymmetry levels do not differ according to the ancestry (African, European or hybrid) of the individuals. Therefore, if ongoing hybridization contributed to increasing the genetic and phenotypic diversity of the populations and influences its adaptive potential, developmental stressors could not be identified and their evolutionary consequences remain uncertain.

Powder bed fusion (PBF) is the most commonly used additive manufacturing process for fabricating complex metal parts via the layer-wise melting of powder. Despite the tremendous recent technological development of PBF, manufactured parts still lack consistent quality in terms of part properties such as dimensional accuracy, surface roughness, or relative density. In addition to process-inherent variability, this is mainly owing to a knowledge gap in the understanding of process influences and the inability to adequately control them during part production. Eddy current testing (ECT) is a well-established nondestructive testing technique primarily used to detect near-surface defects and measure material properties such as electrical conductivity in metal parts. Hence, it is an appropriate technology for the layer-wise measuring of the material properties of the fused material in PBF. This study evaluates ECT’s potential as a novel in situ monitoring technology for relative part density in PBF. Parts made from SS316L and AlSi10Mg with different densities are manufactured on a PBF machine. These parts are subsequently measured using ECT, as well as the resulting signals correlated with the relative part density. The results indicate a statistically significant and strong correlation (316L: r(8) = 0.998, p < 0.001, AlSi10Mg: r(8) = 0.992, p < 0.001) between relative part density and the ECT signal component, which is mainly affected by the electrical conductivity of the part. The results indicate that ECT has the potential to evolve into an effective technology for the layer-wise measuring of relative part density during the PBF process.

Sixty-seven inscriptions have been recorded (42 epitaphs, 21 dedications to deities and 4 varied texts) concerning slaves and freedmen and women. Outside the Collegium venatorum at Deensium 92 individuals have been numbered, or at least probably (64 men, 26 women and 2 anonymous of undetermined sex). There were 23 individual slaves (17 men and 6 women), 69 were freedslaves (47 men, 20 women and 2 anonymous of undetermined sex) – among them 58 freedslaves of Roman citizens (43 men, 15 women) and 11 freedslaves of peregrines (4 men, 5 women and the 2 anonymous). We have in this paper successively studied the documents, the chronological and geographical distribution, the designation, status and functions, the private life, relationship with the master/mistress or patronus/-a, the religious behaviour and taking part to the civic life of slaves and freedslaves of Roman citizens and of peregrines.

Abstract Background The South West Indian Ocean (SWIO) archipelagos and Madagascar constitute a hotspot of biodiversity with a high rate of endemism. In this area, the endemic subspecies A. m. unicolor has been described in Madagascar. It belongs to the African lineage, one of the four described evolutionary lineages in honey bees. Despite a long beekeeping tradition and several recorded European introductions, few studies have been carried out on the diversity and proportion of honey bee subspecies. In order to identify and define which evolutionary lineages and potential sub-lineages are present in the SWIO, the COI-COII intergenic region and the ND2 gene of the mtDNA were sequenced in honey bee colonies from three archipelagos. An extensive sampling (n = 1184 colonies) was done in the Mascarene (La Réunion, Mauritius, Rodrigues), Seychelles (Mahé, Praslin, La Digue) and Comoros (Grande Comore, Mohéli, Anjouan, Mayotte) archipelagos. Islands genetic diversity was compared to newly sampled populations from Madagascar, continental African and European populations. Results African lineage haplotypes were found in all islands (except for Rodrigues). Madagascar, Comoros and Seychelles had 100% of A lineage, 95.5% in La Réunion and 56.1% in Mauritius. Among all African colonies detected in the SWIO, 98.1% (n = 633) of COI-COII haplotypes described the presence of the subspecies A. M. unicolor. Both genetic markers revealed i) a new private AI mitochondrial group shared by the SWIO archipelagos and Madagascar distant from continental populations; ii) the private African haplotypes for each island suggested diversity radiation in the archipelagos; iii) the detection of the Comoros archipelago as a possible contact area between insular and continental African populations. The exotic European C and M lineages were only detected in the Mascarene archipelago, but striking differences of proportion were observed among islands. Merely 4.6% of European colonies were found in La Réunion whereas Mauritius cumulated 44%. Here, among the 84 observed COI-COII haplotypes, 50 were newly described including 13 which were private to the SWIO archipelagos and Madagascar. Similarly, 24 of the 34 found ND2 haplotypes were novel which included six haplotypes particular to the SWIO populations. Conclusion A new African subgroup was described in the SWIO region with mitochondrial genetic evidence that A. m. unicolor is the indigenous subspecies of the archipelagos surrounding Madagascar.

Despite extensive surveys conducted in the past, many remote areas in the Philippines remain unexplored and many species are unknown to science. The Mount Hamiguitan Range (MHR) is among these areas, containing large remaining forests tracts. In this study, we report new records of amphibians and reptiles from MHR and propose removing two species from the previously listed species from this mountain range. We used standardized techniques to sample populations of amphibians and reptiles in fragmented forests of Mt. Hamiguitan. Our survey resulted in 16 new records of species (four frogs, three lizards and nine snakes). Combining our results with previous studies, the known species diversity from the MHR is now increased to a total of 61 taxa. Our results highlight the underestimated diversity of herpetofauna of Mt. Hamiguitan, and we discuss the importance of repeated surveys for determining species occurrences and assessing their conservation status.

With the development of technology and communication nowadays, it encourages everyone to get everything quickly, easily and precisely, especially in the world of e-commerce which is increasingly widespread and needed by almost everyone. A small thing that can help consumers is when they start looking for products or services that are according to their wishes quickly, easily and precisely along with them, assisted by other alternative choices. So when consumers want to type in the product they are looking for, they need to quickly search for synonyms. Autocomplete helps to do that by making search predictions based on the number of products previously purchased.

We report herein the design, synthesis and biological evaluation of new antioxidant and neuroprotective multitarget directed ligands (MTDLs) able to block Ca2+ channels. New dialkyl 2,6-dimethyl-4-(4-(prop-2-yn-1-yloxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate MTDLs 3a−t, resulting from the juxtaposition of nimodipine, a Ca2+ channel antagonist, and rasagiline, a known MAO inhibitor, have been obtained from appropriate and commercially available precursors using a Hantzsch reaction. Pertinent biological analysis has prompted us to identify the MTDL 3,5-dimethyl-2,6−dimethyl−4-[4-(prop−2−yn−1-yloxy)phenyl]-1,4-dihydro- pyridine- 3,5-dicarboxylate (3a), as an attractive antioxidant (1.75 TE), Ca2+ channel antagonist (46.95% at 10 μM), showing significant neuroprotection (38%) against H2O2 at 10 μM, being considered thus a hit-compound for further investigation in our search for anti-Alzheimer’s disease agents.

MJM is a small company that works in the automotive business especially for a two-wheeled vehicle. Nowadays MJM has already using the information system to make the listings for the items, sales, and procurement. When the stock is getting low, MJM orders the item to the supplier but sometimes it’s not optimal because the amount of the items they bought are always too much or too less than the needs, and sometimes they ordered the items on the wrong time. The goal here is to make the owner of the shop able to analyze the optimal amount of items when ordering using the EOQ (Economic Order Quantity) method and to analyze when is the right time to reorder the items using ROP (ReOrder Point), so in the future this application will be useful for the owner.

Bacterial wilt (BW) is a major disease of solanaceous crops caused by the Ralstonia solanacearum species complex (RSSC). Strains are grouped into five phylotypes (I, IIA, IIB, III, and IV). Varietal resistance is the most sustainable strategy for managing BW. Nevertheless, breeding to improve cultivar resistance has been limited by the pathogen’s extensive genetic diversity. Identifying the genetic bases of specific and non-specific resistance is a prerequisite to breed improvement. A major gene (ERs1) was previously mapped in eggplant (Solanum melongena L.) using an intraspecific population of recombinant inbred lines derived from the cross of susceptible MM738 (S) × resistant AG91-25 (R). ERs1 was originally found to control three strains from phylotype I, while being totally ineffective against a virulent strain from the same phylotype. We tested this population against four additional RSSC strains, representing phylotypes I, IIA, IIB, and III in order to clarify the action spectrum of ERs1. We recorded wilting symptoms and bacterial stem colonization under controlled artificial inoculation. We constructed a high-density genetic map of the population using single nucleotide polymorphisms (SNPs) developed from genotyping-by-sequencing and added 168 molecular markers [amplified fragment length polymorphisms (AFLPs), simple sequence repeats (SSRs), and sequence-related amplified polymorphisms (SRAPs)] developed previously. The new linkage map based on a total of 1,035 markers was anchored on eggplant, tomato, and potato genomes. Quantitative trait locus (QTL) mapping for resistance against a total of eight RSSC strains resulted in the detection of one major phylotype-specific QTL and two broad-spectrum QTLs. The major QTL, which specifically controls three phylotype I strains, was located at the bottom of chromosome 9 and corresponded to the previously identified major gene ERs1. Five candidate R-genes were underlying this QTL, with different alleles between the parents. The two other QTLs detected on chromosomes 2 and 5 were found to be associated with partial resistance to strains of phylotypes I, IIA, III and strains of phylotypes IIA and III, respectively. Markers closely linked to these three QTLs will be crucial for breeding eggplant with broad-spectrum resistance to BW. Furthermore, our study provides an important contribution to the molecular characterization of ERs1, which was initially considered to be a major resistance gene.

With globalization the Western honey bee has become a nearly cosmopolitan species, but it was originally restricted to the Old World. This renowned model of biodiversity has diverged into five evolutionary lineages and several geographic "subspecies." If Apis mellifera unicolor is indubitably an African subspecies endemic to Madagascar, its relationship with honey bees from three archipelagos in the southwest Indian Ocean (SWIO) hotspot of biodiversity is misunderstood. We compared recent mtDNA diversity data to an original characterization of the nuclear diversity from honey bees in the Mascarenes and Comoros archipelagos, using 14 microsatellites, but also additional mtDNA tRNALeu-cox2 analysis. Our sampling offers the most comprehensive dataset for the SWIO populations with a total of 3,270 colonies from 10 islands compared with 855 samples from Madagascar, 113 from Africa, and 138 from Europe. Comprehensive mitochondrial screening confirmed that honey bees from La Réunion, Mauritius, and Comoros archipelagos are mainly of African origin (88.1% out of 2,746 colonies) and that coexistence with European lineages occurs only in the Mascarenes. PCA, Bayesian, and genetic differentiation analysis showed that African colonies are not significantly distinct on each island, but have diversified among islands and archipelagos. FST levels progressively decreased in significance from European and African continental populations, to SWIO insular and continental populations, and finally among islands from the same archipelago. Among African populations, Madagascar shared a nuclear background with and was most closely related to SWIO island populations (except Rodrigues). Only Mauritius Island presented clear cytoplasmic disequilibrium and genetic structure characteristic of an admixed population undergoing hybridization, in this case, between A. m. unicolor and A. m. ligustica, A. m. carnica and A. m. mellifera-like individuals. Finally, global genetic clustering analysis helped to better depict the colonization and introduction pattern of honey bee populations in these archipelagos.

After 2007, upsurges of whiteflies on cassava plants and high incidences of cassava diseases were observed in Central African Republic. This recent upsurge in the abundance of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) was directly linked to serious damage to cassava crops resulting from spread of whitefly-borne cassava mosaic geminiviruses (CMGs). There is currently very little information describing whitefly populations on cassava and associated crops in Central African Republic. The current study aimed to address this gap, and to determine whether the increasing damage associated with B. tabaci whiteflies was the consequence of a new invasion, or an upsurge of a local population. The molecular genetic identification and phylogenetic relationships of 898 B. tabaci adult individuals collected from representative locations (54) throughout CAR were determined based on their mitochondrial cytochrome oxidase I sequences (mtCOI). Field and ecological data were also collected from each site, including whitefly abundance, CMD incidence, host plants colonized by B. tabaci and agro-ecological zone. Phylogenetic analysis of the whitefly mtCOI sequences indicated that SSA1 (-SG1, -SG2), SSA3, MED, MEAM1 and Indian Ocean (IO) putative species occur in CAR. One specific haplotype of SSA1-SG1 (SSA1-SG1-P18F5) predominated on most cassava plants and at the majority of sites. This haplotype was identical to the SSA1-SG1 Mukono8-4 (KM377961) haplotype that was recorded from Uganda but that also occurs widely in CMD pandemic-affected areas of East Africa. These results suggest that the SSA1-SG1-P18F5 haplotype occurring in CAR represents a recent invasive population, and that it is the likely cause of the increased spread and severity of CMD in CAR. Furthermore, the high mtDNA sequence diversity observed for SSA1 and its broad presence on all sites and host plants sampled suggest that this genetic group was the dominant resident species even before the arrival of this new invasive haplotype.

Rare literary sources and epigraphy have enabled us to list 178 Vocontii “notables” and members of their families. According to their dignitas they can be divided into five different hierarchical groups: honestiores, priests (except flamines and flaminicae of the imperial cult), local honorati, municipal honorati and “imperial” honorati. Honestiores are significantly fewer than honorati and évergètes (75 out of 178 “notables”). Women (42 in number) are also far behind men (136). Our documentation covers a long period, from 66-65 BC to the second half of the 3rd c. AD, but more than fifth of the inscriptions cannot be dated. 31 “notables” are attested outside their civitas; the rest of them are mainly mentioned in texts found in Luc-en-Diois (Drôme), Die (Drôme) and Vaison-la-Romaine (Vaucluse). Other small towns and rural areas are far less represented. It can be assumed, however, that this privileged society derived the bulk of their wealth from their lands. Most of them were Roman citizens whose names are evidence of their will to integrate the Latin world and Romanitas. The same is true of the 25 peregrini. Their participation in local, municipal and “imperial” life remained constant throughout the Early Empire.

ABSTRACT Plasmodium falciparum malaria remains one of the most deadly infections worldwide. The pathogenesis of the infection results from the sequestration of infected erythrocytes (IRBC) in vital organs, including the brain, with resulting impairment of blood flow, hypoxia, and lactic acidosis. Sequestration occurs through the adhesion of IRBC to host receptors on microvascular endothelium by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large family of variant surface antigens, each with up to seven extracellular domains that can bind to multiple host receptors. Consequently, antiadhesive therapies directed at single endothelial adhesion molecules may not be effective. In this study, we demonstrated that the serine protease thrombin, which is pivotal in the activation of the coagulation cascade, cleaved the major parasite adhesin on the surface of IRBC. As a result, adhesion under flow was dramatically reduced, and already adherent IRBC were detached. Thrombin cleavage sites were mapped to the Duffy binding-like δ1 (DBLδ1) domain and interdomains 1 and 2 in the PfEMP1 of the parasite line IT4var19. Furthermore, we observed an inverse correlation between the presence of thrombin and IRBC in cerebral malaria autopsies of children. We investigated a modified (R67A) thrombin and thrombin inhibitor, hirugen, both of which inhibit the binding of substrates to exosite I, thereby reducing its proinflammatory properties. Both approaches reduced the barrier dysfunction induced by thrombin without affecting its proteolytic activity on PfEMP1, raising the possibility that thrombin cleavage of variant PfEMP1 may be exploited as a broadly inhibitory antiadhesive therapy. IMPORTANCE Plasmodium falciparum malaria is the third leading cause of mortality due to a pathogen, with 214 million people infected and 438,000 deaths annually. The adhesion of Plasmodium falciparum-infected erythrocytes (IRBC) to microvascular endothelium is a major pathological process in severe malaria. While the recent implementation of artemisinin-based antimalarial therapy for severe malaria improves patient survival by targeting all parasite stages, antiparasite drugs alone may not immediately reverse pathophysiological processes in occluded vessels. Here we show that thrombin, an enzyme intimately involved in the clotting process, cleaves the main parasite adhesin expressed on the surface of IRBC, thereby preventing and reversing the binding of IRBC to endothelial cells. This beneficial effect of thrombin can be achieved by modified thrombins that cause significantly less clotting and vessel leakage while preserving the ability to cleave the parasite protein. Our results provide the basis for using modified thrombins as adjunctive therapy in severe malaria.

À partir d’une analyse du concept de diagnostic, cet article tente de cerner l’intérêt qu’il y a à pratiquer une évaluation « diagnostique » des compétences scolaires. L’analyse fait apparaître que le diagnostic peut être envisagé soit comme un constat, soit, en analogie avec le modèle médical, comme une démarche qui remonte de la performance de l’élève à sa compétence. Seul le second sens permet un usage pédagogique et didactique de l’évaluation diagnostique. Cependant, dans ce second cas, la notion de diagnostic implique une saisie de l’élève comme objet à analyser, qui semble incompatible avec la volonté éducative de l’instituer en sujet.

In the last 20 years, molecular ecology approaches have proven to be extremely useful to identify and assess factors associated with viral emerging diseases, particularly in economically and socially important tropical crops such as maize (maize streak disease) and cassava (cassava mosaic disease). Molecular ecology approaches were applied in Reunion Island to analyze the epidemic of tomato yellow leaf curl disease, which has been affecting the island since the end of the 1990s. Before the invasive biotype B (currently known as Middle East-Asia Minor 1 cryptic species) of Bemisia tabaci spread across the world, Reunion Island (South West Indian Ocean) only hosted an indigenous biotype of B. tabaci, Ms (currently known as Indian Ocean cryptic species). Wild hybrids between invasive and indigenous species were subsequently characterized over multiple generations. Endosymbiont analysis of the hybrid population indicated that matings were non-random. Similarly, while no indigenous begomoviruses have ever been reported on Reunion Island, the two main strains of one of the most damaging and emerging plant viruses in the world, the Mild and Israel strains of the Tomato yellow leaf curl virus (TYLCV-Mld and TYLCV-IL), were introduced in 1997 and 2004 respectively. While these introductions extensively modified the agricultural landscape of Reunion Island, they also provided an invaluable opportunity to study the ecological and genetic mechanisms involved in biological invasion and competition.

E-learning content being a barrier for e-learning is no longer true on today’s Internet. The current concerns are how to effectively annotate and organize the available content (both textual and non-textual) to facilitate effective sharing, reusability and customization. In this paper, we explain a component-oriented approach to organize content in an ontology. We also illustrate our 3-tier e-learning content management architecture and relevant interfaces. We use a simple yet intuitive example to successfully demonstrate the current working prototype which is capable of compiling personalized course materials. The e-learning system explained here uses the said ontology.

The temples of the first half of the XIXth century had the neo-classic style, calling reminding the public buildings and the Antiquity. The neogothic style, less good adapted to the worship comes then, under the second Empire. The end of the century sees a more composite style. In the XXth century the figurative pictures begin to appear and the most recent temples sometimes adopt a very original architecture.

Personalization of Ontology Based E-learning System. Today, a form of technology known as Web 2.0 thatthoroughly supports web-to-web interactions is present. Interactions, such as information sharing in the forms ofdocument sharing (slideshare), picture sharing (flickr), video sharing (youtube), Wikis, and online networking (weblogand web-forum) are principally accomodating community empowerment services. These factors cause the appearanceof social interaction through Internet as well as learning interaction and anywhere-anytime training which is recentlycalled e-Learning. Basically, e-Learning needs a self-employed learning method and learning habits that emphasize onthe learner as the most important role. However, e-learning system which is expected to boost the intensity of selfemployedlearning is uncapable to represent the importance. This is proven with the current e-Learning system inIndonesia that only accomodates the delivery of learning materials identical to all active learners, ignores the cognitiveaspects and does not offer any approach or experience of interactive self-learning and disregards the aspect of users’ability to adapt. The proposed e-learning system which is Web 2.0-based utilizes ontology as the representation ofmeaning of knowledge formed by the learner.

This paper analyses the nature and intensity of the functional and institutional integration in three cross-border metropolitan regions in Europe: Basel, Geneva and Luxembourg. Results show that there is not necessarily a reciprocal link between the size of the functional area and the extent of the cooperation. Whilst no metropolitan-sized organisation is on the agenda in Luxembourg, the cases of Basel and Geneva show that the presence of a national border offers an opportunity to invent original forms of governance, increase the autonomy of the local authorities by different types of cooperation which transcend the institutional and territorial divides, and promote the international character of the metropolitan centre. In a context of global competition, these features represent an undeniable benefit.

This article focuses on the way public bodies have invested borders in the European Union and especially how some parts of the limit of sovereignty are transformed into cross-border places in the process of construction of cross-border metropolitan regions. These places, binding two national territories instead of separating or distancing, are the results of cooperation’s projects between territorial authorities on local level. Two projects are analysed: the Garden of the Two Banks in Strasbourg and Kehl between France and Germany achieved in 2004 and the Jacques Delorsplein in Menen and Halluin between Belgium and France, created in 2014.In the first case, the border spaces located on both sides of the Rhine river were regenerated and transformed into a common cross-border recreation and leisure area whose symbolic heart is a pedestrian and bicycle bridge. In the second case, the margin spaces located on the borders between two neighboured municipalities became a public square. The genesis and the reasons of the creation of these two spaces are different, but the comparison is quite relevant considering their transformations into public spaces, their symbolic meaning and the need of cross-border cooperation to ensure the urban management. The ‘refoundation’ of the border area is due to a change of the functions and more deeply in the transformation of its meaning inside the urban area, enabling new people’s space practices. The transformation of the border from articulation or interface to a living space is both the results of cross-border governance and a innovating answer to issues regarded as being similar by the public bodies. The metropolitan context enables to get resources necessary to build the basis of a cooperation and to produce a place in the ‘urban semic system’ which is constructed at cross-border urban scale. The appropriation of these two spaces by the people is still very different. The Garden of the Two Banks is a popular public space in the cross-border urban area of Strasbourg-Kehl while the Jacques Delors square is only the starting point of a regenerated area project.

The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy.

Most aphids are highly specialized on one or two related plant species and generalist species often include sympatric populations adapted to different host plants. Our aim was to test the hypothesis of the existence of host specialized lineages of the aphid Melanaphis sacchari in Reunion Island. To this end, we investigated the genetic diversity of the aphid and its association with host plants by analyzing the effect of wild sorghum Sorghum bicolor subsp. verticilliflorum or sugarcane as host plants on the genetic structuring of populations and by performing laboratory host transfer experiments to detect trade-offs in host use. Genotyping of 31 samples with 10 microsatellite loci enabled identification of 13 multilocus genotypes (MLG). Three of these, Ms11, Ms16 and Ms15, were the most frequent ones. The genetic structure of the populations was linked to the host plants. Ms11 and Ms16 were significantly more frequently observed on sugarcane, while Ms15 was almost exclusively collected in colonies on wild sorghum. Laboratory transfer experiments demonstrated the existence of fitness trade-offs. An Ms11 isofemale lineage performed better on sugarcane than on sorghum, whereas an Ms15 lineage developed very poorly on sugarcane, and two Ms16 lineages showed no significant difference in performances between both hosts. Both field and laboratory results support the existence of host plant specialization in M. sacchari in Reunion Island, despite low genetic differentiation. This study illustrates the ability of asexual aphid lineages to rapidly undergo adaptive changes including shifting from one host plant to another.