Large-scale integration of sequence and structure data in the study of carbonic anhydrase enzymes

In this discovery of carbonic anhydrases, several computational techniques have been used to examine different facets of these enzymes. Methods produced in this work aid for instance in the evaluation of the accuracy of Multiple Sequence Alignments and AlphaFold models, the retrieval of combinations of amino acids from targeted areas of Multiple Sequence Alignments, the evaluation of disulfides and metal-binding residues, the programmatic assessments of molecular geometry, and the production of molecular pictures. Therefore, by utilizing these data mining methods, we have learnt more about the composition, properties, and interactions of carbonic anhydrases, which will help us comprehend these enzymes and their function in biological systems better. Most importantly, the catalytic center and mechanism of the thus far poorly characterized delta carbonic anhydrases has been reliably established. Accordingly, this research offers novelty in several aspects such as combining large-scale data from AlphaFold models, analyzing the reproducibility of functional aspects in AlphaFold models, and formulating theories for the catalytic mechanism of a nearly unknown protein family using features of sequence conservation and structural evaluation

OPTIMIZING THE PISTACHIO SUPPLY CHAIN AND LOGISTICS NETWORK FOR FRESNO COUNTY USING GEOGRAPHIC INFORMATION SYSTEMS NETWORK ANALYSIS METHOD

ABSTRACT Optimizing the Pistachio Supply Chain and Logistics Network for Fresno County Using Geographic Information Systems Network Analysis Method Farnaz Daneshpour This study aims to optimize the transportation of pistachios from orchards to processing centers in Fresno County, California to improve logistics efficiency and reduce environmental impacts. This study evaluates the current transportation situation and compared it with the case in which a new processing center is built. Also, this study evaluates transportation efficiency based on calculations of total driving distance, driving time, fuel cost, and Co2 emission and assesses how much of these variables will be saved if a new facility center is built. This study also explores optimal locations for pistachio cultivation, based on soil characteristics such as soil pH, type, and drainage class and compared these locations to current pistachio orchards. The study is based on data from 52 pistachio orchards in Fresno County, 11 existing large scale processing centers in the Central Valley, the current transportation network, and soil survey data. Location allocation and closest facility analyses using Network Analysis in ESRI ArcGIS are carried out on two scenarios; first for allocation of the orchards to existing processing centers and second, reallocation of orchards considering a new processing facility in the area. A Center of Gravity model is used to determine an optimal location of the new processing facility in Fresno County. Comparing two scenarios shows that there is 41% of saving in distance, Co2 emission, fuel cost, and driving time in a harvesting period by considering the new processing center in Fresno County. Locating the new facility center in the area can make positive improvements towards logistics efficiency and environmental issues

Towards Sustainable Project Governance : A Multisystem and Multilevel Analysis

Multilevel assessment has been put forward in this study as a key tool for tackling the challenges of sustainable development. Therefore, in addition to the micro scale, two other important levels are analysed: the meso and macro levels. Through spatial modelling, this research contributes to the context of project portfolio management and presents a gestalt of systems. The study starts from the analysis of macro scale sustainable development within the European context. Four key elements of the model are introduced: innovation, efficiency, co-creation and environment. This approach also presents a solution to the challenge of the paradigm shift that has increased the complexity of project portfolio management. Subsequently, the front-end of the portfolio has been formulated with a sustainable method. Meanwhile, the trend of eco-efficiency in the EU-15 countries is evaluated, and a longitudinal analysis determines the cases that are promoting sustainability. Furthermore, the challenge of sustainability requires a business model that governs the whole system. Thus, the meso scale has been studied through a systematic review of the literature and exploratory case studies of prominent companies in Europe. Consequently, an open innovation model as a mediator of the Agile method is discussed as a framework. The study gradually narrows down towards the micro scale in Finland. Although the efficiency of various cases has been analysed, another layer of analysis is performed in order to explore the reasons behind the efficiency in Finland. The performances of projects in Finland are assessed through decomposition analysis.Tämä tutkimus esittää monitasoista arviointia keskeiseksi välineeksi kestävän kehityksen haasteiden ratkaisemiseen. Sen johdolla on analysoitu mikrotason lisäksi kahta muuta tärkeää tasoa: meso- ja makrotasoa. Spatiaalisen mallinnuksen avulla tämän tutkimuksen tarkoituksena on edistää projektisalkunhallintaa sekä muodostaa systeemien kokonaisuus. Tutkimus on aloitettu kestävän kehityksen makrotason analyysilla eurooppalaisessa kontekstissa. Mallin neljä keskeistä elementtiä ovat innovaatio, tehokkuus, yhteiskehittäminen ja ympäristö. Tämä lähestymistapa tarjoaa myös ratkaisun paradigman muutoksen aiheuttamalle haasteelle, joka on lisännyt projektisalkunhallinnan monimutkaisuutta. Tämän seurauksena projektisalkun alkuvaihe on muodostettu kestävää menetelmää hyödyntäen. Samalla on arvioitu ekotehokkuuden kehitystä EU-15 maissa sekä pitkittäisanalyysin avulla määritetty ne tapaukset, jotka ovat edistyneet kestävästi. Kestävän kehityksen haasteet vaativat myös liiketoimintamallin, jolla voidaan hallita koko järjestelmää. Siten mesotasoa on tarkasteltu sekä systemaattisen kirjallisuuskatsauksen että merkittävien eurooppalaisten yritysten avulla. Sen seurauksena viitekehityksenä on käsitelty avointa innovaatiomallia ketterän mallin muuntavana tekijänä. Tutkimus kapenee asteittain kohti mikrotasoa Suomessa. Vaikka monien eri tapauksien tehokkuutta onkin jo analysoitu, tehdään toinen analyysi tehokkuuden syiden selvittämiseksi Suomessa. Projektien suorituskykyä Suomessa on arvioitu dekompositioanalyysillä.fi=vertaisarvioitu|en=peerReviewed

Value Generation in Higher Education Space Management Through User-Centric Data Analytics

The space in universities is the most expensive asset. However, there is a clear lack in the literature regarding ‘serendipity’ areas or informal third-places (such as lounges), which host paramount activities in modern Higher Education Institutions (HEI), such as studying, research, teamwork, socializing and networking. This study is the first instance of studying space attributes of lounges and study rooms within universities. Through comparing the instances of low occupancy graduate lounges with the ones highly utilized, the goal is to find the significance of lounge spaces to graduate students, and the impact that proper design can make on their experience. According to this study, noise level and furniture (in terms of comfort and layout) are both the prime and almost equally significant factors to the users. This study identifies the potential to increase occupancy of lounge spaces within Texas A&M University up to three times through noise limitation and furniture improvement. Further studies are required for more accurate forecasting of the influence of such factors for decision making in higher education space management. This may help universities to allocate proper efficient serendipity spaces to their graduate students, which could bring value to both students and institutions, not only academically, but also financially

Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme:a potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis

Introduction to Multiple Dimensions of a Responsive Public Space; A case study in Iran

Člankom se pokušava definirati novi model funkcionalnoga javnog prostora s ključnom ulogom u zadovoljavanju ljudskih potreba. S tim u vezi anketa intervjuom provedena je sa 120 ispitanika. Model funkcionalnoga javnog prostora u konačnici definiraju četiri vida odgovornosti, i to fizičkim aspektima prostora, aktivnostima, značenjem te društvenim aspektima, od kojih svaki posjeduje specifične značajke. Rezultati također pokazuju da je među svim aspektima fizički najvažniji.This paper tries to define a new model of responsive public space that can play a key role in meeting human needs. In this regard, personal interviews were conducted with 120 participants. The model of responsive public space was defined by four aspects of responsibility that include the physical, social, activity and meaning factors, each with its own special indicators. These results show that the physical factor has the highest importance among the four aspects of responsibility

Explaining the Relationship between Changes in Iranian Lifestyle and Metamorphosis of Urban Form of Residential Environment in Contemporary Iran Case Study: Mashhad, Iran

[EN] Humanity settlement are formed as a result of decisions and actions of different people and become as a form of an identity of integrity. So urban form is influenced by desires, values, beliefs, and human activities, so the study of urban form is the study of its constituent human values and expression of physical aspects of their lifestyles. Before contemporary periods, urban form in Iran, continuity based on former patterns of changes, which was gradual, but after the beginning of the influence of west, one of the most important challenges of urban form in Iran is in the form of short-term changes. Changes occur in a cycle of destruction and construction. This paper use the way of content analysis investigate to texts, document to study form and typo-morphology of residential environment in the city of Mashhad. In the periods of one hundred years shows there is a direct and significant relationship between changes of Iranian lifestyle and metamorphosis of urban form, so that by sequential developments of Iranian lifestyle in a short time, the urban form is responded and metamorphosed and again is created in a new form.Abedzadeh, A.; Daneshpour, A.; Ostadi, M. (2018). Explaining the Relationship between Changes in Iranian Lifestyle and Metamorphosis of Urban Form of Residential Environment in Contemporary Iran Case Study: Mashhad, Iran. En 24th ISUF International Conference. Book of Papers. Editorial Universitat Politècnica de València. 285-298. https://doi.org/10.4995/ISUF2017.2017.5705OCS28529

Value Generation in Higher Education Space Management Through User-Centric Data Analytics

The space in universities is the most expensive asset. However, there is a clear lack in the literature regarding ‘serendipity’ areas or informal third-places (such as lounges), which host paramount activities in modern Higher Education Institutions (HEI), such as studying, research, teamwork, socializing and networking. This study is the first instance of studying space attributes of lounges and study rooms within universities. Through comparing the instances of low occupancy graduate lounges with the ones highly utilized, the goal is to find the significance of lounge spaces to graduate students, and the impact that proper design can make on their experience. According to this study, noise level and furniture (in terms of comfort and layout) are both the prime and almost equally significant factors to the users. This study identifies the potential to increase occupancy of lounge spaces within Texas A&M University up to three times through noise limitation and furniture improvement. Further studies are required for more accurate forecasting of the influence of such factors for decision making in higher education space management. This may help universities to allocate proper efficient serendipity spaces to their graduate students, which could bring value to both students and institutions, not only academically, but also financially

Global community effect: large-scale cooperation yields collective survival of differentiating embryonic stem cells [preprint]

“Community effect” conventionally describes differentiation occurring only when enough cells help their local (micrometers-scale) neighbors differentiate. Although new community effects are being uncovered for myriad differentiations, macroscopic-scale community effects - fates of millions of cells all entangled across centimeters - remain elusive. We found that differentiating mouse Embryonic Stem (ES) cells that are scattered as individuals over many centimeters form one macroscopic entity via long-range communications. The macroscopic population avoids extinction only if its centimeter-scale density is above a threshold value. Single-cell-level measurements, transcriptomics, and mathematical modeling revealed that this “global community effect” occurs because differentiating ES-cell populations secrete, accumulate, and sense survival-promoting factors, including FGF4, that diffuse over many millimeters and activate Yap1-induced survival mechanisms. Only above-threshold-density populations accumulate above-threshold-concentrations of factors required to survive. We thus uncovered a previously overlooked, large-scale cooperation that underlies ES-cell differentiation. Tuning such large-scale cooperation may enable constructions of macroscopic, synthetic multicellular structures