1,287 research outputs found

    UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4

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    UBR4 is a 574 kDa E3 ligase (E3) of the N-degron pathway with roles in neurodevelopment, age-associated muscular atrophy and cancer. The catalytic module that carries out ubiquitin (Ub) transfer remains unknown. Here we identify and characterize a distinct E3 module within human UBR4 consisting of a ‘hemiRING’ zinc finger, a helical-rich UBR zinc-finger interacting (UZI) subdomain, and an N-terminal region that can serve as an affinity factor for the E2 conjugating enzyme (E2). The structure of an E2–E3 complex provides atomic-level insight into the specificity determinants of the hemiRING toward the cognate E2s UBE2A/UBE2B. Via an allosteric mechanism, the UZI subdomain modestly activates the Ub-loaded E2 (E2∌Ub). We propose attenuated activation is complemented by the intrinsically high lysine reactivity of UBE2A, and their cooperation imparts a reactivity profile important for substrate specificity and optimal degradation kinetics. These findings reveal the mechanistic underpinnings of a neuronal N-degron E3, its specific recruitment of UBE2A, and highlight the underappreciated architectural diversity of cross-brace domains with Ub E3 activity.</p

    Constructing a profile for proactive career self-management in public higher education institutions in Ghana

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    Text in English with abstracts and keywords in English, isiXhosa, and isiZuluThe principal focus of this research study was to investigate the relationship among psychosocial career pre-occupation, social connectedness, and organisational commitment, and to determine whether an overall proactive career management profile can be constructed to inform career self-management practices in public higher education institutions (HEIs) in Ghana. Again, the research study intended to provide a background for testing hypotheses and theories as well as moderating the effect of socio-demographic characteristics (age, gender, marital status and job level) on the relationship between psychosocial career pre-occupations, social connectedness and organisational commitment. A cross-sectional quantitative approach was conducted on a purposively selected sample of senior staff comprising academic and administrative staff (n = 288), from a single public higher educational institution in Ghana. The measuring instruments include a career pre-occupations inventory workplace friendship scale and an organisational commitment scale. Descriptive statistics (mean, standard deviation, skewness and kurtosis), bi-variate correlation analysis (Pearson product moment correlation coefficient), and inferential and multivariate statistics (SEM analysis, moderated regression analysis, ANOVAs and independent sample t-test) were used for the study. Descriptive, bi-variate correlation and inferential statistics revealed that individual psychosocial career pre-occupations, social connectedness and organisational commitment can be used as elements within a proactive career self-management framework within the Ghanaian higher education institutions. The results of the moderated analysis showed that respondents’ gender and job level moderated employees’ level of psychosocial career pre-occupations in predicting organisational commitment. Furthermore, the test for significant mean differences revealed that gender, marital status and job level differed marginally in their psychosocial career pre-occupations, social connectedness and commitment to the organisation. Theoretically and empirically, the results advanced the career construction theory by empirically validating the core elements of career self-management. Practically, a recommendation was made to inform human resource (HR) managers and HR practitioners in public higher education institutions in Ghana and the consequences indicated in the study offer the opportunity to monitor and provide strategies and interventions for employees in their quest for career choices.Ugqaliselo oluphambili kolu phononongo lophando yayikukuphanda ubudlelwane phakathi komsebenzi wangaphambi kwekhondo ngokwesimo sengqondo nangokwezentlalo (psychosocial career pre-occupation), ukuziphatha, nokunxulumana kwezinto zokuziphatha nezentlalo (social connectedness), kunye nokuzibophelela kulungelelaniso /kucwangciso lombutho (organisational commitment), nokuqonda ukuba ingaba iprofayili yeendlela zokulawula ikhondo elisebenzayo elipheleleyo inokwakhelwa ukwazisa izenzo zekhondo lomsebenzi lokuzilawula kumaziko emfundo ephakamileyo karhulumente/oluntu (HEIs) eGhana. Kwakhona , uphononongo lophando lwaluzimisele ukunikezela ngomhlaba osisiseko wokuvavanya ingcinga ethathwa njengeyinyaniso engekaqinisekiswa (hypothesis) neethiyori kwakunye nokumodereyitha impembelelo yeempawu zedemografi yoluntu, i-socio-demographic characteristics (iminyaka, isini, imeko yomtshato,kunye nenqanaba lomsebenzi) kubudlelwane phakathi kwemisebenzi yangaphambi kwekhondo nemeko yezengqondo nabantu (psychosocial career pre-occupations), unxulumano lwabantu kunye nokuzibophelela kumbutho (organizational commitment). Inkqubo yophando ngokobungakanani enqamlezileyo ngokwamacandelo ahlukeneyo (cross sectional quantitative approach) yenziwe kwisampulu ekhethwe ngenjongo kujoliswe kubasebenzi abaphezulu/abadala ababandakanya izifundiswa nabasebenzi bezolawulo (n = 288), besuka kwiziko elinye loluntu lemfundo ephakamileyo eGhana. Izixhobo zokulinganisa zibandakanya uluhlu lwezinto kwisikali semisebenzi yangaphambi kwekhondo ubudlelwane kunye nokuzibophelela kumbutho kwindawo yokusebenzela. Iinkcukacha-manani ezichazayo (i-avareji, ukutenxa kumgangatho (standard deviation), ubugoso (skewness) kunye nomlinganiselo weenkcukacha-manani osetyenziselwa ukuchaza ukuhanjiswa kwedatha ephawulweyo malunga nentsingiselo (kurtosis), uhlalutyo lolungelelwaniso oluphindwe kabini kunye neenkcukacha-manani ezinokuthelelelekwa (i- Pearson product moment correlation coefficient), kunye neenkcukacha manani ezizintlobo-ntlobo ezininzi ezinokuthelekelelwa (uhlalutyo lwe-SEM, uhlalutyo oluhlehlayo olonganyelweyo/ olumodareyithiweyo, i-ANOVA kunye novavanyo oluzimeleyo lwe-t-test) zasetyenziswa kolu phando/phononongo. Inkcukacha-manani ezichazayo, ulungelelwaniso/unxulumaniso oluphindwe kabini kunye nezinokuthelekelelwa ezinentsingiselo zibonise ukuba imisebenzi yangaphambi kwekhondo,ngokwemeko yengqondo neyentlalo, unxulumano lwentlalo yoluntu kunye nokuzibophelela kumbutho kunokusetyenziswa njengezinto ezingaphakathi kwesakhelo solawulo esisebenzayo ngaphakathi kumaziko emfundo ephakamileyo yaseGhana.Iziphumo zohlalutyo olumodareyithiweyo zibonise ukuba isini sabaphenduli nenqanaba lomsebenzi samodareyitha inqanaba labasebenzi kwimisebenzi yangaphambi kwekhondo kwimeko yengqondo nezentlolontle ekuqikeleleni ukuzibophelela kumbutho. Ngaphaya koko, uvavanyo olubalulekileyo lweeyantlukwano lubonise ukuba isini, meko yomtshato kunye nenqanaba lomsebenzi lahlukile kancinci ngokwe-avareji kwimisebenzi yaphambi kwekhondo labo yengqondo nentlalontle, unxibelelwano lwentlalo kunye nokuzinikela embuthweni. Ngokwethiyori nangobungqina, iziphumo ziqhubele phambili ithiyori yolwakhiwo lwekhondo lomsebenzi ngokuqinisekisa ngobuchule izinto ezingundoqo zokuzilawula kwekhondo lomsebenzi.Ngokwenene, kwenziwa isindululo sokwazisa abaphathi bezabasebenzi neengcali ze-HR kumaziko emfundo ephakamileyo yoluntu eGhana kwaye iziphumo ezibonakaliswe kuphononongo zinika ithuba lokubeka esweni nokubonelela ngezicwangciso-qhinga nongenelelo ngoncedo kubaqeshwa kwiphulo labo lokukhetha amakhondo omsebenzi.Lesi sifundo socwaningo sasigxile kakhulu ekuphenyeni ngobudlelwano phakathi kokucabanga ngomkhakha womsebenzi komuntu, ukuxhumana nabantu, ukuzibophezela komuntu emsebenzini, kanye nokunquma ukuthi iphrofayili yokukwazi ukuzilawula ngokuzenzela ekukhetheni umkhakha womsebenzi kungahlelwa yini ngendlela yokuthi kudlale indima ekuzilawuleleni maqondana nomkhakha womsebenzi ezikhungweni zezemfundo ephakeme zomphakathi (ama-HEI) eGhana. Kanti futhi, isifundo socwaningo sihlose ukunikeza umlando maqondana nokuhlola imicabango kanye nemibono yezinjulalwazi kanjalo nokulinganisa umphumela wezici zokuhleleka kwabantu emphakathini (iminyaka yobudala, ubulili, isimo somshado kanye nezinga lomsebenzi) ebudlelwaneni phakathi kokucabanga ngomkhakha womsebenzi komuntu, ukuxhumana nabantu, kanye nokuzibophezela emsebenzini. Kwalandelwa indlela yokubheka isibalo samaqoqo abantu emphakathini ngokukhetha ngokuqaphela isampula labasebenzi abasezikhundleni eziphezulu elibandakanya abasebenza ngezemfundo kanye nezokuphatha (n = 288), esikhungweni sezemfundo ephakeme somphakathi esisodwa eGhana. Amathuluzi okukala afaka kuwo isilinganiso sobungane basemsebenzini ekukhetheni ezinhlobeni zemikhakha ecatshangwayo kanye nesilinganiso maqondana nokuzibophezela kwabantu emsebenzini. Kulolu cwaningo kwasetshenziswa izibalo ezichazayo (okujwayelekile, ukuphambuka okuvamile, ukungalingani kanye nobukhali), ukuhlaziywa kokuhlobana okukhona phakathi kwezinombolo ezimbili (isilinganiso sokuxhumana kwezinombolo ezimbili ngokukaPearson), kanye nezibalo eziveza izimbangela nezibalo ezahlukahlukene (ukuhlaziywa kwe-SEM, ukuhlaziywa kokubuyelamuva okulingene, ama-ANOVA kanye nesampula elizimele lokuhlola). Izibalo ezichazayo, eziveza ukuhlobana phakathi kwezinombolo ezimbili kanye nezibalo eziveza izimbangela ziveze ukuthi ukucabanga ngomkhakha womsebenzi komuntu ngamunye, ukuxhumana nabantu nokuzibophezela emsebenzini kungasetshenziswa njengezinto ezikhona ohlakeni lokukwazi ukuzilawula ngokuzenzela ekukhetheni umkhakha ezikhungweni zezemfundo ephakeme zaseGhana. Imiphumela yokuhlaziywa okulingene yakhombisa ukuthi ubulili bababambiqhaza kanye nezinga labo ngokwezikhundla zomsebenzi kuhambisana nezinga abasebenzi abacabanga ngalo nomkhakha womsebenzi ekuqageleni indlela abazozibophezela ngayo emsebenzini. Ngaphezu kwalokho, ukuhlolwa komehluko omkhulu ojwayelekile kwaveza ukuthi ubulili, isimo somshado kanye nezinga ngokwesikhundla somsebenzi kwahluka kakhulu nendlela abacabanga ngayo ngomkhakha womsebenzi, ukuxhumana nabantu nokuzibophezela emsebenzini. Ngokombono wenjulalwazi nocwaningo olufakazelwe, imiphumela ithuthukise umbono wenjulalwazi wokuhlela umkhakha womsebenzi okuqinisekiswe ngokocwaningo olufakazelwe izinto ezinqala zokuzilawulela umkhakha womsebenzi. Ekusebenzeni, kwenziwa izincomo zokufundisa abaphathi babasebenzi (ba-HR) kanye nabasebenza ngezabasebenzi (ngezakwa-HR) ezikhungweni zezemfundo ephakeme zomphakathi eGhana, kanti nemiphumela evezwe ocwaningweni inikeza ithuba lokuqapha nokuhlinzeka amasu kanye nokungenelela kwabasebenzi ekwenzeni kwabo izinqumo zomsebenzi.Business ManagementPh. D. (Business Management

    Tools for efficient Deep Learning

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    In the era of Deep Learning (DL), there is a fast-growing demand for building and deploying Deep Neural Networks (DNNs) on various platforms. This thesis proposes five tools to address the challenges for designing DNNs that are efficient in time, in resources and in power consumption. We first present Aegis and SPGC to address the challenges in improving the memory efficiency of DL training and inference. Aegis makes mixed precision training (MPT) stabler by layer-wise gradient scaling. Empirical experiments show that Aegis can improve MPT accuracy by at most 4\%. SPGC focuses on structured pruning: replacing standard convolution with group convolution (GConv) to avoid irregular sparsity. SPGC formulates GConv pruning as a channel permutation problem and proposes a novel heuristic polynomial-time algorithm. Common DNNs pruned by SPGC have maximally 1\% higher accuracy than prior work. This thesis also addresses the challenges lying in the gap between DNN descriptions and executables by Polygeist for software and POLSCA for hardware. Many novel techniques, e.g. statement splitting and memory partitioning, are explored and used to expand polyhedral optimisation. Polygeist can speed up software execution in sequential and parallel by 2.53 and 9.47 times on Polybench/C. POLSCA achieves 1.5 times speedup over hardware designs directly generated from high-level synthesis on Polybench/C. Moreover, this thesis presents Deacon, a framework that generates FPGA-based DNN accelerators of streaming architectures with advanced pipelining techniques to address the challenges from heterogeneous convolution and residual connections. Deacon provides fine-grained pipelining, graph-level optimisation, and heuristic exploration by graph colouring. Compared with prior designs, Deacon shows resource/power consumption efficiency improvement of 1.2x/3.5x for MobileNets and 1.0x/2.8x for SqueezeNets. All these tools are open source, some of which have already gained public engagement. We believe they can make efficient deep learning applications easier to build and deploy.Open Acces

    Data ethics : building trust : how digital technologies can serve humanity

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    Data is the magic word of the 21st century. As oil in the 20th century and electricity in the 19th century: For citizens, data means support in daily life in almost all activities, from watch to laptop, from kitchen to car, from mobile phone to politics. For business and politics, data means power, dominance, winning the race. Data can be used for good and bad, for services and hacking, for medicine and arms race. How can we build trust in this complex and ambiguous data world? How can digital technologies serve humanity? The 45 articles in this book represent a broad range of ethical reflections and recommendations in eight sections: a) Values, Trust and Law, b) AI, Robots and Humans, c) Health and Neuroscience, d) Religions for Digital Justice, e) Farming, Business, Finance, f) Security, War, Peace, g) Data Governance, Geopolitics, h) Media, Education, Communication. The authors and institutions come from all continents. The book serves as reading material for teachers, students, policy makers, politicians, business, hospitals, NGOs and religious organisations alike. It is an invitation for dialogue, debate and building trust! The book is a continuation of the volume “Cyber Ethics 4.0” published in 2018 by the same editors

    Spatiotemporal analysis of transcription dynamics

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    Energy Supplies in the Countries from the Visegrad Group

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    The purpose of this Special Issue was to collect and present research results and experiences on energy supply in the Visegrad Group countries. This research considers both macroeconomic and microeconomic aspects. It was important to determine how the V4 countries deal with energy management, how they have undergone or are undergoing energy transformation and in what direction they are heading. The articles concerned aspects of the energy balance in the V4 countries compared to the EU, including the production of renewable energy, as well as changes in its individual sectors (transport and food production). The energy efficiency of low-emission vehicles in public transport and goods deliveries are also discussed, as well as the energy efficiency of farms and energy storage facilities and the impact of the energy sector on the quality of the environment

    Supporting Custom Instructions with the LLVM Compiler for RISC-V Processor

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    The rise of hardware accelerators with custom instructions necessitates custom compiler backends supporting these accelerators. This study provides detailed analyses of LLVM and its RISC-V backend, supplemented with case studies providing end-to-end overview of the mentioned transformations. We discuss that instruction design should consider both hardware and software design space. The necessary compiler modifications may mean that the instruction is not well designed and need to be reconsidered. We discuss that RISC-V standard extensions provide exemplary instructions that can guide instruction designers. In this study, the process of adding a custom instruction to compiler is split into two parts as Assembler support and pattern matching support. Without pattern matching support, conventional software requires manual entries of inline Assembly for the accelerator which is not scalable. While it is trivial to add Assembler support regardless of the instruction semantics, pattern matching support is on the contrary. Pattern matching support and choosing the right stage for the modification, requires the knowledge of the internal transformations in the compiler. This study delves deep into pattern matching and presents multiple ways to approach the problem of pattern matching support. It is discussed that depending on the pattern's complexity, higher level transformations, e.g. IR level, can be more maintainable compared to Instruction Selection phase.Comment: Electronics and Communication Engineering B.Sc. Graduation Project. Source can be found in https://github.com/eymay/Senior-Design-Projec

    Re-emergence of Neglected Tropical Diseases amid the COVID-19 Pandemic : Epidemiology, Transmission, Mitigation Strategies, and Recent Advances in Chemotherapy and Vaccines

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    The current re-emergence of neglected tropical diseases (NTD) amid the global COVID-19 pandemic requires increased attention. These include communicable and vector-borne diseases caused by various fungi, bacteria (e.g. tuberculosis), viruses (e.g. dengue, Chikungunya fever, monkeypox, Marburg and Ebola virus disease, poliomyelitis, rabies), and parasites (e.g. filariasis, malaria, trypanosomiasis, leishmaniasis, schistosomiasis, onchocerciasis). Whilst the vast majority of such diseases remain endemic to specific regions of the world (e.g. tropical Africa), some - like those caused by the Ebola virus, the Marburg virus, and more recently the Monkeypox virus - have been reported elsewhere (e.g. Europe and America), forcing public health boards in various countries to take all necessary precautions to control such a spread. The Department for Control of Neglected Tropical Disease was created in 2005 by the World Health Organization (WHO) to tackle NTD. In 2021, the 74th World Health Assembly proposed a 9-year plan (2021-2030) intended to eradicate neglected diseases. Over the past three years, COVID-19 has had a significant impact on socio-economic activities and healthcare systems worldwide. With the WHO recently declaring the global monkeypox outbreak a Public Health Emergency of International Concern, a coordinated effort among high-income and low/middle-income countries is now more than ever recommended to address the threat posed by the worldwide re-emergence of some NTD. There is currently a lack of knowledge on understanding how such diseases are transmitted and what mitigation strategies should be put in place to control their spread. Better availability of diagnostic tests, vaccines, and drugs in affected countries is also required. In this Research Topic, we wish to address how to best tackle the re-emergence of NTD in the context of the COVID-19 pandemic. This collection welcomes a range of articles including opinion, commentary, systematic reviews, and original research articles on epidemiology, transmission, mitigation strategies, and recent advances in chemotherapy and vaccines for these NTD

    Modeling and Simulation in Engineering

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    The Special Issue Modeling and Simulation in Engineering, belonging to the section Engineering Mathematics of the Journal Mathematics, publishes original research papers dealing with advanced simulation and modeling techniques. The present book, “Modeling and Simulation in Engineering I, 2022”, contains 14 papers accepted after peer review by recognized specialists in the field. The papers address different topics occurring in engineering, such as ferrofluid transport in magnetic fields, non-fractal signal analysis, fractional derivatives, applications of swarm algorithms and evolutionary algorithms (genetic algorithms), inverse methods for inverse problems, numerical analysis of heat and mass transfer, numerical solutions for fractional differential equations, Kriging modelling, theory of the modelling methodology, and artificial neural networks for fault diagnosis in electric circuits. It is hoped that the papers selected for this issue will attract a significant audience in the scientific community and will further stimulate research involving modelling and simulation in mathematical physics and in engineering

    Bio-inspired optimization in integrated river basin management

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    Water resources worldwide are facing severe challenges in terms of quality and quantity. It is essential to conserve, manage, and optimize water resources and their quality through integrated water resources management (IWRM). IWRM is an interdisciplinary field that works on multiple levels to maximize the socio-economic and ecological benefits of water resources. Since this is directly influenced by the river’s ecological health, the point of interest should start at the basin-level. The main objective of this study is to evaluate the application of bio-inspired optimization techniques in integrated river basin management (IRBM). This study demonstrates the application of versatile, flexible and yet simple metaheuristic bio-inspired algorithms in IRBM. In a novel approach, bio-inspired optimization algorithms Ant Colony Optimization (ACO) and Particle Swarm Optimization (PSO) are used to spatially distribute mitigation measures within a basin to reduce long-term annual mean total nitrogen (TN) concentration at the outlet of the basin. The Upper Fuhse river basin developed in the hydrological model, Hydrological Predictions for the Environment (HYPE), is used as a case study. ACO and PSO are coupled with the HYPE model to distribute a set of measures and compute the resulting TN reduction. The algorithms spatially distribute nine crop and subbasin-level mitigation measures under four categories. Both algorithms can successfully yield a discrete combination of measures to reduce long-term annual mean TN concentration. They achieved an 18.65% reduction, and their performance was on par with each other. This study has established the applicability of these bio-inspired optimization algorithms in successfully distributing the TN mitigation measures within the river basin. Stakeholder involvement is a crucial aspect of IRBM. It ensures that researchers and policymakers are aware of the ground reality through large amounts of information collected from the stakeholder. Including stakeholders in policy planning and decision-making legitimizes the decisions and eases their implementation. Therefore, a socio-hydrological framework is developed and tested in the Larqui river basin, Chile, based on a field survey to explore the conditions under which the farmers would implement or extend the width of vegetative filter strips (VFS) to prevent soil erosion. The framework consists of a behavioral, social model (extended Theory of Planned Behavior, TPB) and an agent-based model (developed in NetLogo) coupled with the results from the vegetative filter model (Vegetative Filter Strip Modeling System, VFSMOD-W). The results showed that the ABM corroborates with the survey results and the farmers are willing to extend the width of VFS as long as their utility stays positive. This framework can be used to develop tailor-made policies for river basins based on the conditions of the river basins and the stakeholders' requirements to motivate them to adopt sustainable practices. It is vital to assess whether the proposed management plans achieve the expected results for the river basin and if the stakeholders will accept and implement them. The assessment via simulation tools ensures effective implementation and realization of the target stipulated by the decision-makers. In this regard, this dissertation introduces the application of bio-inspired optimization techniques in the field of IRBM. The successful discrete combinatorial optimization in terms of the spatial distribution of mitigation measures by ACO and PSO and the novel socio-hydrological framework using ABM prove the forte and diverse applicability of bio-inspired optimization algorithms
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