Molecular cloning of a novel human I-mfa domain-containing protein that differently regulates human T-cell leukemia virus type I and HIV-1 expression.

Regulation of viral genome expression is the result of complex cooperation between viral proteins and host cell factors. We report here the characterization of a novel cellular factor sharing homology with the specific cysteine-rich C-terminal domain of the basic helix-loop-helix repressor protein I-mfa. The synthesis of this new factor, called HIC for Human I-mfa domain-Containing protein, is controlled at the translational level by two different codons, an ATG and an upstream non-ATG translational initiator, allowing the production of two protein isoforms, p32 and p40, respectively. We show that the HIC protein isoforms present different subcellular localizations, p32 being mainly distributed throughout the cytoplasm, whereas p40 is targeted to the nucleolus. Moreover, in trying to understand the function of HIC, we have found that both isoforms stimulate in T-cells the expression of a luciferase reporter gene driven by the human T-cell leukemia virus type I-long terminal repeat in the presence of the viral transactivator Tax. We demonstrate by mutagenesis that the I-mfa-like domain of HIC is involved in this regulation. Finally, we also show that HIC is able to down-regulate the luciferase expression from the human immunodeficiency virus type 1-long terminal repeat induced by the viral transactivator Tat. From these results, we propose that HIC and I-mfa represent two members of a new family of proteins regulating gene expression and characterized by a particular cysteine-rich C-terminal domain.

Key locations for soybean genotype assessment in Central Brazil

The objective of this work was to identify key locations for the establishment of soybean (Glycine max) genetic breeding programs, in the Central Region of Brazil. Grain yield data of three maturity groups of soybean genotypes, from regional trials conducted over three years, at 18 locations in Brazilian Cerrado were used. A key location for the early phases of the breeding program was defined as the site that best classifies the winning genotypes in the region. Key locations for the final phases were defined as those sites that best represent each environmental stratum, in relation to the adaptability of the respective winning genotype. This adaptability was estimated by additive main effects and multiplicative interaction (AMMI) model analysis, using the distance between the score of each location in a stratum and the score of the winning genotype, which characterizes such stratum in an AMMI biplot. The locations that best classified the winning genotypes over space and time were Mineiros, Placas and Rio Verde. For the final phases of genotype selection, with data from the three maturity group, the recommended locations were: Buritis, Chapadão do Céu, Iraí, Pamplona, Placas, Planaltina, Rio Verde, Sacramento, Senador Canedo, Uberaba, and Uberlândia.

Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR.

Agua, basuras y alcantarillado: reciprocidad y políticas ambientales en un suburbio brasileño

The main purpose ofthis work is to analyse the relationship existing between reciprocity and moral by studying the main sanitation system, the drinking water supply, the sewerage, the drainage andgarbage collecting in a brasilian suburb. We agree with the hypothesis that the lack ofbasic sanitation and/ or aprecarious system genérate certain way of social exchange related to the system of circulation and distribution ofgoods andservices between people and the household units and to local political actions associatedto some ideas about moral andpoor people justice.

Toiminnan kehittäminen ohutlevykonepajassa

Yritysmaailma elää jatkuvassa muutoksessa. Yrityksen kehittäminen on yrityksen menestymisen kannalta välttämätöntä. Mikäli yritystä ei aktiivisesti kehitetä, kilpailijat valtaavat yrityksen elintilan ja yritys taantuu ja lopulta yrityksen toiminta lakkaa. Tämän työn tarkoituksena oli kehittää Compusteel Oy:n toimintaa ja edistää yhtiön kilpailukykyä lähitulevaisuudessa. Compusteel Oy on luonteeltaan alihankkija / komponenttitoimittaja. Tällaisen yrityksen tärkein kilpailutekijä on tehokas tuotanto. Tässä työssä keskityttiin tutkimaan erityisesti keinoja, millä tuotantoa voidaan tehostaa. Useissa työn lähteenä käytetyissä tutkimuksissa on havaittu tiedon välittämisen merkitys nykyaikaisen yrityksen kilpailutekijänä. Tyypillisimmillään toiminnan virheet johtuvat tiedon puutteellisesta välittämisestä sekä tiedon käytettävyyden heikosta tasosta tarvetilanteessa. Tutkimus toteutettiin kirjallisuuden ja muun lähdeaineiston kuten koulutusten avulla. Tutkimuksessa paneuduttiin erityisesti erilaisten tuotannonohjausmenetelmien kartoittamiseen sekä niiden hyödyntämiseen yrityksen toiminnassa. Työn tuloksena syntyi Compusteel Oy:öön uusi toimintamalli tiettyihin yrityksen ydin prosesseihin. Erityisen tärkeänä nähtiin uuden ajattelumallin omaksuminen tuotannonohjaushenkilöstössä. Uutta ajattelumallia voidaan tulevaisuudessa soveltaa useissa yrityksen kehittämishankkeissa. Lisäksi työn tuloksena käyttöönotettiin uusi toiminnanohjausjärjestelmä, joka tukee uutta toimintamallia.

Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.

Acid-sensing ion channels (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function.

Centre d'assitència primària CAP Concòrdia a Sabadell

Award-winning

Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução

The chemotherapy agents against cancer may be classified as "cell cycle-specific" or "cell cycle-nonspecific". Nevertheless, several of them have their biological activity related to any kind of action on DNA such as: antimetabolic agents (DNA synthesis inhibition), inherently reactive agents (DNA alkylating electrophilic traps for macromolecular nucleophiles from DNA through inter-strand cross-linking - ISC - alkylation) and intercalating agents (drug-DNA interactions inherent to the binding made due to the agent penetration in to the minor groove of the double helix). The earliest and perhaps most extensively studied and most heavily employed clinical anticancer agents in use today are the DNA inter-strand cross-linking agents.

Percutaneous access versus standard femoral exposure for endovascular abdominal aortic aneurysm repair: a randomized, controlled trial

The treatment of abdominal aortic aneurysm (AAA) has shifted from the exposure of the aorta artery in an open repair technique to a small groin cut in an endovascular repair. Recently, a percutaneous access for endovascular repair has appeared. This new technique aims to minimize the complications of the common femoral artery exposure, the patient discomfort and the length of hospitalizationObjectives: To compare the proportion of discharged patients within the first 48 postoperative hours of two common femoral artery accesses for endovascular repair of AAA: the open exposure technique and the percutaneous technique. Secondary objectives include to evaluate the total procedure time, the femoral access complications, the need for extra analgesia and the patient satisfaction and groin discomfort of the two techniquesDesign: Randomized controlled trial conducted between 2014 and 2017Participants: Patients diagnosed with abdominal aortic aneurysm with elective endovascular repair indication

Teknologiansiirto vuorovaikutuksena yliopistojen ja yritysten välillä - Systemaattinen kirjallisuuskatsaus

Tutkielman tavoitteena oli selvittää teknologiansiirrosta vuorovaikutusnäkökulmasta tehdyt empiiriset tutkimukset systemaattisen kirjallisuuskatsauksen avulla. Teoreettinen näkökulma perustui vuorovaikutteisten innovaatioverkostojen rakentamista yliopistojen, yritysten ja valtion välille korostavaan Triple Helix -viitekehykseen. Valtion ohjaava rooli rajattiin tutkielman ulkopuolelle. Tutkimuskysymykset olivat miten teknologiansiirtoa on empiirisesti tutkittu yliopistojen ja yritysten välisenä vuorovaikutuksena, mitkä ovat yliopistojen ja yritysten väliset vuorovaikutusmuodot ja miten teknologiansiirtoa kannattaisi tutkia. Tutkimuksista koostuva aineisto hankittiin systemaattisella kirjallisuushaulla. Aineisto rajattiin teknologiansiirtoa vuorovaikutusnäkökulmasta tutkineisiin empiirisiin tutkimuksiin. Analysointimenetelmänä käytettiin sisällönanalyysiä. Tulosten perusteella teknologiansiirron tutkimisen teoreettisia lähestymistapoja olivat yrittäjyyssuuntautuneisuuteen yliopistoissa kannustava ”entrepreneurial university” -suuntaus, innovaatiot ja innovaatiojärjestelmät, tutkijoiden ominaisuudet ja sosiaalinen pääoma, vuorovaikutus- ja tiedonsiirtoprosessit, organisationaalinen oppiminen ja yliopiston teknologiansiirtopolitiikat. Teknologiansiirtoa oli tutkittu enemmän yliopisto- kuin yritysnäkökulmasta. Tutkimuksista puolet otti huomioon hiljaisen tiedon siirrettävyyden vain vuorovaikutuksen avulla. Tutkielman tuloksena tunnistettiin 34 erilaista vuorovaikutusmuotoa teknologiansiirrossa yliopistojen ja yritysten välillä. Tutkituimmat vuorovaikutusmuodot olivat patentit ja lisenssit, asiantuntija-apu ja konsultointi, epämuodolliset kontaktit ja verkostot, yliopistojen spin-off-yritykset ja sopimustutkimus. Tutkimusyhteistyötä oli tutkittu suhteellisen vähän. Teknologiansiirron tehokkuutta kannattaisi tutkia yritysnäkökulmasta selvittämällä tutkimusyhteistyön ja innovaatioiden välinen yhteys. Teknologiansiirtoa vuorovaikutusprosessina kannattaisi tutkia kaikkien siihen osallistuvien sidosryhmien näkökulmista. Teknologiansiirtoprojektien onnistumiseen vaikuttavia tekijöitä voisi selvittää vertailevien tapaustutkimusten avulla. Tiedonsiirtoprosessiin liittyvää vuorovaikutusta ei prosessina kannattaisi tutkia irrallisena ilmiönä siihen liittyvistä tiedonsiirto-olosuhteista. Vuorovaikutusmuotojen määrä suomalaisessa teknologiansiirrossa olisi tutkimisen arvoinen asia. Vuorovaikutusmuotojen lukumäärän selvittämisellä voisi arvioida yhteistyösuhteen syvyyttä yliopistojen ja yritysten välillä. Yritykset tulisi nähdä aktiivisina toimijoina teknologiansiirrossa, ja teknologiansiirtoa tulisi tutkia myös yritysten näkökulmasta.

Achieving competitive e-commerce in Finnish B2C retail business

E-commerce is one of the most fast growing business areas today and an extremely important channel in retail. In order for companies to succeed in this business environment, it is highly important to understand consumers and how they perceive and select webstores. The objective of the study is to investigate how to achieve competitive e-commerce by investigating consumers and the factors based on which they select a webstore. In addition, the study also seeks to explore whether sex or consumers’ buying experience have an effect on consumer’s webstore selection. Managerial implications are viewed from case company’s perspective. In order to answer the research questions a quantitative marketing survey was conducted. The data was collected by online questionnaire using the case company’s customers as respondents. A total of 1613 responses were obtained from Finnish consumers. Responses were analyzed using ANOVA, factor analysis and t-test. The results show that the most important factors in consumer’s webstore selection are usability, reliability and vendor related information. The biggest difference between heavy and light shoppers is trust formation. Light shoppers value physical stores and familiar vendors, whereas heavy shoppers judge vendor based on the information and usability. Women perceive higher risk than men. The winning strategy requires a hybrid of cost leadership and differentiation.

Dynamic capabilities as enablers of value co-creation between an MBA school and its students

This study presents an understanding of how a U.S. based, international MBA school has been able to achieve competitive advantage within a relatively short period of time. A framework is built to comprehend how the dynamic capability and value co-creation theories are connected and to understand how the dynamic capabilities have enabled value co-creation to happen between the school and its students, leading to such competitive advantage for the school. The data collection method followed a qualitative single-case study with a process perspective. Seven semi-structured interviews were made in September and October of 2015; one current employee of the MBA school was interviewed, with the other six being graduates and/or former employees of the MBA school. In addition, the researcher has worked as a recruiter at the MBA school, enabling to build bridges and a coherent whole of the empirical findings. Data analysis was conducted by first identifying themes from interviews, after which a narrative was written and a causal network model was built. Thus, a combination of thematic analysis, narrative and grounded theory were used as data analysis methods. This study finds that value co-creation is enabled by the dynamic capabilities of the MBA school; also capabilities would not be dynamic if value co-creation did not take place. Thus, this study presents that even though the two theories represent different level analyses, they are intertwined and together they can help to explain competitive advantage. The MBA case school’s dynamic capabilities are identified to be the sales & marketing capabilities and international market creation capabilities, thus the study finds that the MBA school does not only co-create value with existing students (customers) in the school setting, but instead, most of the value co-creation happens between the school and the student cohorts (network) already in the recruiting phase. Therefore, as a theoretical implication, the network should be considered as part of the context. The main value created seem to lie in the MBA case school’s international setting & networks. MBA schools around the world can learn from this study; schools should try to find their own niche and specialize, based on their own values and capabilities. With a differentiating focus and a unique and practical content, the schools can and should be well-marketed and proactively sold in order to receive more student applications and enhance competitive advantage. Even though an MBA school can effectively be treated as a business, as the study shows, the main emphasis should still be on providing quality education. Good content with efficient marketing can be the winning combination for an MBA school.

Geography Football Team

The winning intramural football team from the Geography department. Pictured from left to right are: Brian Rogers, Lino Fuciarelli, Tim Slack, Les Selby, Larry Miller, Bob Lunge (captain), Ron Devereux, Bob Steele, and Gerry Gamble.

Investigation of single tryptophan proteins encapsulated in TEOS-derived sol-gel matrices by fluorescence spectroscopy /

In the work reported here, optically clear, ultrathin TEOS derived sol-gel slides which were suitable for studies of tryptophan (Trp) fluorescence from entrapped proteins were prepared by the sol-gel technique and characterized. The monitoring of intrinsic protein fluorescence provided information about the structure and environment of the entrapped protein, and about the kinetics of the interaction between the entrapped protein and extemal reagents. Initial studies concentrated on the single Trp protein monellin which was entrapped into the sol-gel matrices. Two types of sol-gel slides, termed "wet aged", in which the gels were aged in buffer and "dry-aged", in which the gels were aged in air , were studied in order to compare the effect of the sol-gel matrix on the structure of the protein at different aging stages. Fluorescence results suggested that the mobility of solvent inside the slides was substantially reduced. The interaction of the entrapped protein with both neutral and charged species was examined and indicated response times on the order of minutes. In the case of the neutral species the kinetics were diffusion limited in solution, but were best described by a sum of first order rate constants when the reactions occurred in the glass matrix. For charged species, interactions between the analytes and the negatively charged glass matrix caused the reaction kinetics to become complex, with the overall reaction rate depending on both the type of aging and the charge on the analyte. The stability and conformational flexibility of the entrapped monellin were also studied. These studies indicated that the encapsulation of monellin into dry-aged monoliths caused the thermal unfolding transition to broaden and shift upward by 14°C, and causedthe long-term stability to improve by 12-fold (compared to solution). Chemical stability studies also showed a broader transition for the unfolding of the protein in dry-aged monoliths, and suggested that the protein was present in a distribution of environments. Results indicated that the entrapped proteins had a smaller range of conformational motions compared to proteins in solution, and that entrapped proteins were not able to unfold completely. The restriction of conformational motion, along with the increased structural order of the internal environment of the gels, likely resulted in the improvements in themial and long-term stability that were observed. A second protein which was also studied in this work is the metal binding protein rat oncomodulin. Initially, the unfolding behavior of this protein in aqueous solution was examined. Several single tryptophan mutants of the metal-binding protein rat oncomodulin (OM) were examined; F102W, Y57W, Y65W and the engineered protein CDOM33 which had all 12 residues of the CD loop replaced with a higher affinity binding loop. Both the thermal and the chemical stability were improved upon binding of metal ions with the order apo < Ca^^ < Tb^"^. During thermal denaturation, the transition midpoints (Tun) of Y65W appeared to be the lowest, followed by Y57W and F102W. The placement of the Trp residue in the F-helix in F102W apparently made the protein slightly more thermostable, although the fluorescence response was readily affected by chemical denaturants, which probably acted through the disruption of hydrogen bonds at the Cterminal end of the F-helix. Under both thermal and chemical denaturation, the engineered protein showed the highest stability. This indicated that increasing the number of metal ligating oxygens in the binding site, either by using a metal ion with a higher coordinatenumber (i.e. Tb^*) which binds more carboxylate ligands, or by providing more ligating groups, as in the CDOM33 replacement, produces notable improvements in protein stability. Y57W and CE)OM33 OM were chosen for further studies when encapsulated into sol-gel derived matrices. The kinetics of interaction of terbium with the entrapped proteins, the ability of the entrapped protein to binding terbium, as well as thermal stability of these two entrapped protein were compared with different levels of Ca^"*^ present in the matrix and in solution. Results suggested that for both of the proteins, the response time and the ability to bind terbium could be adjusted by adding excess calcium to the matrix before gelation. However, the less stable protein Y57W only retained at most 45% of its binding ability in solution while the more stable protein CDOM33 was able to retain 100% binding ability. Themially induced denaturation also suggested that CDOM33 showed similar stability to the protein in solution while Y57W was destabilized. All these results suggested that "hard" proteins (i.e. very stable) can easily survive the sol-gel encapsulation process, but "soft" proteins with lower thermodynamic stability may not be able to withstand the sol-gel process. However, it is possible to control many parameters in order to successfully entrap biological molecules into the sol-gel matrices with maxunum retention of activity.

Photograph - Dorothy Rungeling with Husband Charlie and Son Barry, 1953

A photograph of Dorothy Rungeling with husband Charlie and son Barry with the winning trophy of the Governor General's Cup Air Race, Toronoto, 1953.