Event-Object Reasoning with Curated Knowledge Bases: Deriving Missing Information

The broader goal of our research is to formulate answers to why and how questions with respect to knowledge bases, such as AURA. One issue we face when reasoning with many available knowledge bases is that at times needed information is missing. Examples of this include partially missing information about next sub-event, first sub-event, last sub-event, result of an event, input to an event, destination of an event, and raw material involved in an event. In many cases one can recover part of the missing knowledge through reasoning. In this paper we give a formal definition about how such missing information can be recovered and then give an ASP implementation of it. We then discuss the implication of this with respect to answering why and how questions.Comment: 13 page

Financial Management of the Small Municipalities of Nepal: Sustainability Issues

Due to the centre dominated intergovernmental fiscal relation; the decentralization efforts of Nepal remained incomplete even after 9 years of the implementation of LSGA. The financial health of Nepalese local governments, particularly small municipalities is vulnerable as they are going to loose a big chunk of resource called LDF in near future and so far no substitute for it is prescribed or recommended. Many researchers have argued that the proper implementation of property based tax could replace the LDF but there are many concerns and several barriers with such tax system. Firstly it has limited scope to improve the financial health of those municipalities and secondly there are many obstacles: tax culture of the local people, weak institutional capabilities, absence of proper database, untrained human resource and rampant corruption are few of them. Nevertheless, the municipalities have distinct comparative and competitive advantages, which should be explored and implemented accordingly

Translation in Nepal

Panel: Translation/Writing Across Language

EXPERIMENTS AND MODELING OF PLASTIC ANISOTROPY AND DUCTILE FRACTURE UNDER MULTIAXIAL LOADING

The implementation of new materials for light-weighting purposes in the automotive industry has often been hindered due to the low ductility of these materials, as well as inadequate empirical knowledge about their fracture behavior and inadequate material modeling techniques. This thesis addresses these issues through extensive experimental and numerical study of plastic anisotropy and ductile fracture of several aluminum alloys and a stainless-steel. The test materials used for this study include AA365 die-casting, AA6013 and AA6111 aluminum sheets, AA6260 aluminum tube and SS304L stainless-steel microtube. The plastic anisotropy is assessed using uniaxial tension, plane-strain tension and disc compression experiments for the die-casting and the sheets; and using biaxial experiments for the tubes. These experiments are then used to model the anisotropic plastic behavior of the test materials using advanced non-quadratic anisotropic yield criteria including Yld2000-2D and Yld2004-3D. The fracture behavior of the casting and sheets is investigated using conventional notched tension and central hole specimens, as well as novel specimen designs for shear and biaxial stress states. These improved specimen designs exhibit stress states that develop at the neighborhood of the fracture initiation point to remain proportional throughout the loading history. Likewise, the fracture behavior of the tubes is assessed by loading them under axial force and internal pressure along different stress paths. The ability to control the force/pressure ratio enables probing the fracture behavior under proportional and non-proportional loading paths. Fracture oftentimes initiate at the interior (for example through-thickness mid-plane) of the specimens and thus direct measurement of fracture parameters i.e., stress triaxiality, Lode angle parameter and equivalent plastic strain is not possible from experiments alone. Instead, these parameters at the onset of fracture are obtained in this work using finite element modeling with the material modeling framework using anisotropic yield criteria described above. The loading path and the resulting fracture locus are found to be sensitive to the constitutive model employed, which underscores the importance of an appropriate modeling of plastic anisotropy in ductile fracture studies. Based on the finite element results, the fracture locus is represented by numerous fracture initiation criteria common in literature (e.g., Oyane, Johnson-Cook, Hosford-Coulomb and DF2015), as well as a newly proposed one, created during the course of this research, that is shown to offer better agreement with the experiments, without additional calibration or implementation cost

Histopathological analysis of breast lump in an urban community hospital laboratory

Introductions: Breast lump is mostly benign in nature however carcinoma ofthe breast also presents as a simple lump. Since breast carcinoma is the secondmost common killer of the female cancer it is important to detect it at earlystage and treat. The purpose of the study was to analyse histopathology profileof breast lump.Methods: Histopathology samples were received, processed, reported andrecorded in the Pathology laboratory of Helping Hands Community Hospital,Kathmandu. Data analysed from 2008 to 2011. Descriptive statistics was usedto analyse the data.Results: Out of 1991 histopathology samples 68 were breast lumps. Fifty(73.5%) were benign and 18 (26.5%) were malignant. Ten (55.5%) of carcinoma was seen in between 41 and 50 years. Eleven (46%) of the malignant neoplasm were of Stage IIIA.Conclusions: Every fourth sample had carcinoma and it is mostly seen after 40years of age.Keywords: biopsy, breast lump, carcinoma, fibroadenom

Jugaad Culture Amidst COVID-19: A Time to Step Up for Innovation in Low-Income Countries.

More than four months have already elapsed after the world first encountered Coronavirus claimed to originate from Wuhan, China. Scientifically, termed sudden acute respiratory syndrome corona virus (SARS-CoV-2), that causes Coronavirus disease of 2019 (COVID-19), this deadly pathogen has already claimed about 2.83 lakhs casualties with four million infected and 1.5 million recovered as of 11 May 2020. Different preventive measures like hand washing, social distancing, nation-wide lock down from March 23 have been practised inNepal which has definitely dwindled the number of positive cases. they have helped flatten the curve and procure time for preparation for forthcoming disaster. Total documented positive cases have been 120 till date (11 May 2020) with zero mortality in Nepal. However, the scenario might be out of control in coming days where claims of inadequate testing due to lack of diagnostic kits have been a major issue. Whatever be the outcome in upcoming days, for an economically poor country like Nepal, preparation seems satisfactory despite challenges to outsourcing the necessary kits like Personal Protective Equipment (PPE) and diagnostic Polymerase Chain Reaction (PCR) machines etc

Metabolic pathway engineering of actinomycetes for novel antibiotics discovery

Microbes harbouring a profound wealth of chemical space have instigated tremendous attention for developing crucial therapeutic drugs. The genes encoding the enzymes responsible for synthesizing these specialized metabolites are often organized in so-called biosynthetic gene clusters (BGCs). While these clusters are potentially capable of producing novel drug candidate, most of them remain dormant in natural environmental conditions (or settings). Microorganisms seldom synthesize substantial quantities of the desired molecules in natural settings. Harnessing the dormant compound production requires careful optimization of the host cellular machinery, which can be accomplished by thorough engineering of silent biosynthetic pathways. My target, the genus Streptomyces is endowed with tremendous abilities to secrete a diverse array of metabolites. Besides, insilico analysis of their genomic sequences reveals enormous potential to generate novel metabolites not biosynthesized in natural environmental settings. Realizing such bountiful resources, I attempt to unveil Streptomyces’ true potential to generate novel metabolites by using various approaches. In the present dissertation, various novel approaches have allowed me to unveil novel specialized metabolites encoded by otherwise silent biosynthetic clusters. For this, (i) I developed single cell mutant selection (SCMS) platform, where mutants harboring a silent promoter are probed with a double reporter system using classical mutagenesis techniques. Mutants were sorted using FACS based on expression of reporter genes and mutants generated a novel metabolite with a distinct chemical scaffold, referred to as mutaxanthene. (ii) Next approach involved binary physical interaction studies between dead yeast and Streptomyces where the contact induced production of prodigiosin. My studies identified a master-regulator, namely mbkZ, for its regulatory roles in prodigiosin production in different hosts (S. coelicolor and Streptomyces sp. MBK6). (iii) Third approach exploited CRISPR/Cas9 system to unveil the functional role of sdmA within the showdomycin biosynthetic pathway. (iv) Final approach revealed the characterization of new bacterial lineage (Streptomonospora sp. PA3) isolated from the high-salt environment, which helped me to isolate and identify a novel polyketide persiamycin A. Using these different approaches allowed me to unveil the secret knowledge sealed within biosynthetic pathways of the studied organisms. In a nutshell, adopting these techniques has helped me discover and characterize novel metabolites. I believe these strategies may aid in the fight against antimicrobial resistance and speed up the drug discovery process. Furthermore, this dissertation has not only implications for future engineering of Streptomyces to increase metabolites production, but it also illustrates a SCMS state-of-art approach for generating novel therapeutic leads.Aktinomykeettien aineenvaihduntareittien muokkaus uusien antibioottien löytämiseksi Mikrobien tuottamat monimuotoiset luonnonyhdisteet ovat herättäneet suurta kiinnostusta lääkekehityksessä. Näiden erikoistuneiden metaboliittien tuotannosta vastaavia entsyymejä koodaavat geenit ovat yleensä järjestyneet niin sanottuiksi biosynteettisiksi geeniryppäiksi (BGC, engl. biosynthetic gene cluster). Nämä geeniryppäät saattavat tuottaa vielä tuntemattomia metaboliitteja, mutta yleensä ne ovat hiljaisia luonnollisessa ympäristössä. Yleensä mikro-organismit eivät tuota haluttua yhdistettä merkittäviä määriä luonnollisissa olosuhteissa. Näiden hiljaisten yhdisteiden hyödyntäminen lääkeaineiden kehityksessä vaatii solukoneiston huolellista optimointia, mikä voidaan saavuttaa muokkaamalla hiljaisia biosynteesireittejä. Kohdeorganismimme Streptomyces -bakteerit kykenevät tuottamaan lukuisia erilaisia sekundäärimetaboliitteja, jotka ovat kemialliselta rakenteeltaan erittäin vaihtelevia. Tämän lisäksi genomisekvenssien analyysi on paljastanut lukuisia lupaavia hiljaisia geeniklustereita, jotka saattaisivat aktivoituina tuottaa aikaisemmin tuntemattomia yhdisteitä. Tämän työn tarkoitus on käyttää useita erilaisia tekniikoita tämän hiljaisen biosynteettisen potentiaalin valjastamiseen. Väitöskirjatyössä käytin useita uusia menetelmiä hiljaisten geeniryppäiden koodaamien uusien yhdisteiden tuottamiseksi. Tätä tarkoitusta varten (i) kehitin yksisolujen mutanttivalinta (SCMS, engl. single cell mutant selection) alusta – menetelmän, missä hiljaisen geeniryppään aktiivisuutta seurataan tuplareportterisysteemillä. Seuloin menetelmällä mutanttikirjastoja reportterigeenien ilmenemisen perusteella FACS –laitteistoilla ja tuotin erityisen kemiallisen rakenteen omaavia mutaxanthene -yhdisteitä. (ii) Seuraavaksi tutkin hiivojen ja streptomykeettien fyysisen vuorovaikutuksen vaikutusta prodigiosiini –yhdisteen tuottoon. Tutkimukseni paljasti säätelygeeni mbkZ:n roolin prodigiosiinien tuotossa kahdessa eri isäntäkannassa (S. coelicolor ja Streptomyces sp. MBK6). iii) Kolmannessa menetelmässä käytin CRISPR/Cas9-menetelmää selvittääkseni sdmA geenin roolin showdomysiinin biosynteesireitillä. iv) Viimeisenä menetelmänä eristin uuden halofiilisen bakteerikannan (Streptomonospora sp. PA3) korkean suolapitoisuuden kasvuympäristöstä meren pohjasta. Kannasta eristettiin uusi persiamysiini A polyketidi. Näiden erilaisten lähestymistapojen avulla pystyin paljastamaan tutkittujen organismien biosynteettisten reittien sisälle suljetut salaisuudet. Lyhyesti, olemme pystyneet löytämään ja karakterisoimaan uusia metaboliitteja käyttämiemme tekniikoiden avulla. Uskomme, että käyttämämme strategiat auttavat kamppailuissa antibioottiresistenssiä vastaan ja nopeuttamaan uusien lääkkeiden löytämistä. Tämän lisäksi tutkielman tulokset sekä auttavat sekundaarimetabolliittien tuotannon tehostamista tulevaisuudessa streptomykeettejä muokkaamalla, että havainnollistaa SCMS –menetelmän käyttökelpoisuuden uusien terapeuttisten yhdisteiden tuotossa