The Regulation of Skeletal and Cardiac Muscle Blood Flow in Humans. Studies by positron emission tomography with special reference to exercise, adenosine and nitric oxide

Virtually every cell and organ in the human body is dependent on a proper oxygen supply. This is taken care of by the cardiovascular system that supplies tissues with oxygen precisely according to their metabolic needs. Physical exercise is one of the most demanding challenges the human circulatory system can face. During exercise skeletal muscle blood flow can easily increase some 20-fold and its proper distribution to and within muscles is of importance for optimal oxygen delivery. The local regulation of skeletal muscle blood flow during exercise remains little understood, but adenosine and nitric oxide may take part in this process. In addition to acute exercise, long-term vigorous physical conditioning also induces changes in the cardiovasculature, which leads to improved maximal physical performance. The changes are largely central, such as structural and functional changes in the heart. The function and reserve of the heart’s own vasculature can be studied by adenosine infusion, which according to animal studies evokes vasodilation via it’s a_2A receptors. This has, however, never been addressed in humans in vivo and also studies in endurance athletes have shown inconsistent results regarding the effects of sport training on myocardial blood flow. This study was performed on healthy young adults and endurance athletes and local skeletal and cardiac muscle blod flow was measured by positron emission tomography. In the heart, myocardial blood flow reserve and adenosine A_2A receptor density, and in skeletal muscle, oxygen extraction and consumption was also measured. The role of adenosine in the control of skeletal muscle blood flow during exercise, and its vasodilator effects, were addressed by infusing competitive inhibitors and adenosine into the femoral artery. The formation of skeletal muscle nitric oxide was also inhibited by a drug, with and without prostanoid blockade. As a result and conclusion, it can be said that skeletal muscle blood flow heterogeneity decreases with increasing exercise intensity most likely due to increased vascular unit recruitment, but exercise hyperemia is a very complex phenomenon that cannot be mimicked by pharmacological infusions, and no single regulator factor (e.g. adenosine or nitric oxide) accounts for a significant part of exercise-induced muscle hyperemia. However, in the present study it was observed for the first time in humans that nitric oxide is not only important regulator of the basal level of muscle blood flow, but also oxygen consumption, and together with prostanoids affects muscle blood flow and oxygen consumption during exercise. Finally, even vigorous endurance training does not seem to lead to supranormal myocardial blood flow reserve, and also other receptors than A_2A mediate the vasodilator effects of adenosine. In respect to cardiac work, atheletes heart seems to be luxuriously perfused at rest, which may result from reduced oxygen extraction or impaired efficiency due to pronouncedly enhanced myocardial mass developed to excel in strenuous exercise.

Det var intressant, man måste tänka så mycket : öppna laborationer och V-diagram i kemiundervisningen

Laborationerna utgör i många skolor inom den grundläggande utbildningen en självklar del av kemiundervisningen. Laborationerna är vanligen formulerade som ”recept” och eleverna skall följa en given beskrivning då de genomför laborationen. Kravet på eget tänkande från elevernas sida kan härigenom bli litet. Laborationerna är därför utsatta för en hel del kritik på olika håll i världen, därför att de anses ineffektiva ur lärande-synvinkel. S.k. öppna laborationer är en annan typ av laboration som innebär att eleverna ställs inför ett problem eller en utmaning. Eleverna skall själva inom sin laborationsgrupp komma underfund med och planera hur de skall genomföra laborationen. Denna form av laborationer ställer andra krav på elevernas tänkande än traditionella ”kokbokslaborationer”. I denna studie har elever i en klass i årskurs 7 under sin första kemikurs arbetat med öppna laborationer. Laborationerna har av klassens lärare formulerats som utmaningar för eleverna. Eleverna har som ett hjälpverktyg under laborationen använt s.k. V-diagram. V-diagram utgör ett grafiskt verktyg som kan användas som en laborationsrapport. I V-diagrammet synliggörs de olika momenten som ingår i en laboration eller i en undersökning. Vilken är forskningsfrågan, hur planerar man att söka svar på sin fråga, vilka resultat har man kommit till och vilka slutsatser kan man dra? V-diagrammet innehåller också en teoretisk och begreppslig sida där laborationens teoretiska förankring synliggörs. Resultaten från undersökningen visar att arbetet med öppna laborationer i kombination med V-diagram hade positiv inverkan på elevernas uppfattning om sitt eget lärande. Eleverna upplevde att laborationerna krävde tänkande men att detta samtidigt ledde till förståelse. Eleverna hjälpte varandra att försöka förstå då de gemensamt skulle lösa problem. I diskussionen med sina kamrater och med läraren fick eleverna möjlighet att formulera sina egna uppfattningar och konfrontera dem mot andra uppfattningar. V-diagrammets struktur fungerade som vägledning då eleverna planerade sin laboration, men gav också en överblick över laborationer i efterhand då eleverna förberedde sig inför kursprovet, vilket för en del elever bidrog till deras förståelse. Grupperna var i allmänhet mycket fokuserade på uppgiften då de planerade en öppen laboration. Laborationerna hade alla en förankring i vardagen vilket gjorde att eleverna kunde göra kopplingar mellan sina egna erfarenheter och laborationen. Majoriteten av eleverna uppgav efter kemikursen att de upplevt den som intressant och laborationerna lyftes fram speciellt. De öppna laborationerna ställde stora krav på laborationsgrupperna och på elevernas samarbetsförmåga och gjorde laborationerna känsliga för grupprelaterade problem, genom att eleverna skulle klara av utmaningar gemensamt. För en elev med svag självuppfattning kan tillrättalagda laborationer med klara instruktioner kännas tryggare än en öppen laboration, där utmaningen är större. Samtidigt hade just utmaningarna, som var på en nivå som eleverna klarade av efter att ha tänkt och diskuterat med varandra, en positiv inverkan på självuppfattningen för ett flertal av eleverna. Att klara av utmaningar på rätt nivå kan inverka positivt på den egna själuppfattningen. De öppna laborationerna ställer krav på läraren att vara flexibel och kunna gå in i rollen av bl.a. handledare och coach. Samtidigt utgör lärare en representant för det naturvetenskapliga samfundet och har ansvar för att göra teori och begrepp tillgängliga för eleverna då de behöver dessa i sina undersökningar. För lärare kan de öppna laborationerna kännas problematiska, eftersom de själva sällan har erfarenheter av denna typ av laborationer från sin egen skoltid eller utbildning.

Fibroblast Growth Factor 8 and its Receptors in The Growth and Angiogenesis of Experimental Breast Cancer . With Special Reference to Thrombospondin-1 as a Novel Target Gene for FGF-8

The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.

Singular Reference Without Singular Thought

Abstract In this paper I challenge the widespread assumption that the conditions for singular reference are more or less the same as the conditions for singular thought. I claim that we refer singularly to things without thinking singularly about them more often than it is usually believed. I first argue that we should take the idea that singular thought is non-descriptive thought very seriously. If we do that, it seems that we cannot be so liberal about what counts as acquaintance; only perception (and memory) will do. I also briefly discuss and reject semantic instrumentalism. Finally, I argue that while singular reference is cheap, singular thought comes only at a price.

Customer reference marketing and utilization of social media as an integral part of customer references

The objective of this Bachelor's Thesis is to find out the role of social media in the B-to-B marketing environment of the information technology industry and to discover how IT-firms utilize social media as a part of their customer reference marketing. To reach the objectives the concepts of customer reference marketing and social media are determined. Customer reference marketing can be characterized as one of the most practically relevant but academically relatively overlooked ways in which a company can leverage its customers and delivered solutions and use them as references in its marketing activities. We will cover which external and internal functions customer references have, that contribute to the growth and performance of B-to-B firms. We also address the three mechanisms of customer reference marketing which are 'status transfer', 'validation through testimonials' and 'demonstration of experience and prior performance'. The concept of social media stands for social interaction and creation of user-based content which exclusively occurs through Internet. The social media are excellent tools for networking because of the fast and easy access, easy interaction and vast amount of multimedia attributes. The allocation of social media is determined. The case company helps clarify the specific characteristics of social media usage as part of customer-reference-marketing activities. For IT-firms the best channels to utilize social media in their customer reference marketing activities are publishing and distribution services of content and networking services.

Segregation of powder mixtures in silos with particular reference to dry mineral-based construction materials

Segregering eller segregation är ett fenomen som kan förekomma inom olika områden av samhället. Inom samhällsvetenskaperna kan segregering definieras som det rumsliga åtskiljandet av befolkningsgrupper på urval av ras eller etniskt ursprung, kön, social härkomst, religion, ålder, yrke, osv. Segregering av befolkningsgrupper sker ofta mer eller mindre frivilligt och är motsatsen till integration. Inom partikelteknologi definieras segregering oftast som det rumsliga åtskiljandet av beståndsdelarna i en blandning av olika partiklar. Segregering sker då på urval av bl.a. partiklarnas storlek, densitet, form, elektrostatiska eller mekaniska egenskaper, och kan beskrivas som motsatsen till blandning. Segregeringsmekanismer används för att förklara hur och varför en partikelblandning segregerar samt vad slutresultatet i form av den rumsliga fördelningen av partiklarna blir till följd av att blandningen utsetts för en viss behandling. I denna avhandling har segregering av partikelblandningar och speciellt torra mineralbaserade byggmaterial (t.ex. murbruk) till följd av lagring i siloer studerats. Vid industriell produktion av mineralbaserade byggmaterial används siloer för korttidslagring av slutprodukterna precis innan förpackning. Segregering leder till kraftiga variationer i sammansättningen för partikelströmmen ut ur silon, vilket gör att slutprodukterna inte uppfyller kvalitetskraven och kan därmed inte säljas till kunder. Detta leder till arbetsam och dyr bearbetning (återcirkulation) av produkterna med påföljder för produktionsekonomin samt hållbara utvecklingen. I avhandlingen identifierades de väsentligaste segregeringsmekanismerna för torra mineralbaserade byggmaterial i siloer. Dessutom klargjordes effekterna av materialegenskaper, processbetingelser och siloparametrar. Slutligen behandlas möjliga åtgärder för minskning av partikelsegregering i siloer samt tillämpning av matematiska metoder för simulering av partikelflöden med hjälp av datorer.

Factors Affecting Cancer Behavior with Special Reference to Lymphatic Vessels, Macrophages, EGFR, and Pim-1 in Colorectal Cancer

Syövän käyttäytymiseen ja ennusteeseen vaikuttavat monet tekijät, muun muassa muutokset syöpäsoluissa sekä kasvainta ympäröivässä mikroympäristössä. Tutkimuksen tavoitteena oli tutkia uusia prediktiivisiä ja prognostisia ennustetekijöitä syöpäsoluissa (EGFR geenikopiomäärä, EGFR, onkogeeni pim-1) sekä syöpäkasvaimen mikroympäristöön kuuluvissa imuteissä (CLEVER-1, podoplaniini), makrofageissa (CD68, CLEVER-1) ja T lymfosyyteissä (CD3) kolorektaalisyövässä. Lisäksi tutkittiin imuteiden molekulaarisia ominaisuuksia tarkemmin (CD73, LYVE-1, podoplaniini) kuten myös lymfosyyttien ja dendriittisolujen liikennöintiä imuteissä. Tutkimustulokset osoittavat että korkea Pim-1 ekspressiotaso, suuri peritumoraalinen CD68+ makrofagimäärä sekä varhaisen vaiheen taudissa suuri CLEVER-1+ peritumoraalinen makrofagimäärä ovat hyvän ennusteen tekijöitä kolorektaalisyövässä. Metastaattisessa taudissa sen sijaan suuri määrä CLEVER-1+ makrofageja, sekä intra- että peritumoraalisesti, liittyy huonoon tautiennusteeseen. EGFR geenikopiomäärä, EGFR proteiinipitoisuuden ohjaaman hopea in situ hybridisaatiomenetelmän avulla määritettynä, ennusti vastetta anti-EGFR hoidolle metastaattisessa kolorektaalisyövässä tarkemmin kuin nykyisin rutiinisti käytössä oleva KRAS määritys. Lisäksi havaittiin että imutiet ovat monimuotoisia imutiemarkkeri ekspressionsa suhteen sekä normaali- että syöpäkudoksissa. CD73 molekyylin funktio imuteissä poikkesi selvästi molekyylin funktiosta verisuonissa. Yhteenvetona voidaan todeta että kolorektaalisyövän ennusteeseen vaikuttavien tekijöiden merkitys vaihtelee taudin levinneisyysasteen sekä imuteiden että makrofagien sijainnin perusteella. Korkea Pim-1 ilmentyminen on yhteydessä hyvään kolorektaalisyöpäennusteeseen. Lisäksi EGFR geenikopiomäärä osoittautui lupaavaksi uudeksi prediktiiviseksi ennustetekijäksi KRAS villintyypin metastaattista kolorektaalisyöpää sairastavilla potilailla.

Marketing in the pre-development process of agricultural machines: a reference model

The theme of the research is the development of the domain of marketing knowledge in the design of agricultural machinery. It is developed throughout the design of agricultural machinery in order to identify the corporate and customers needs and to develop strategies to satisfy these needs. The central problem of the research questions which marketing tools to apply on pre-development process of farm machinery, in order to increase the market value of the products and of the company and, consequently, generate competitive advantage to the manufacturers of agricultural machinery. As methodology, it was developed bibliographical research and multicase study of the development process of agricultural machinery developed by small, medium and large companies and the academy. As a result, a marketing reference model was elaborated for the pre-development stage of agricultural machinery, which outlines the activities, tasks, mechanisms and controls that can be used in strategic planning and in products planning of agricultural machinery manufacturers, contributing to explain the explicit knowledge in the marketing field.

Evaluation of empirical methods to estimate reference evapotranspiration in Uberaba, State of Minas Gerais, Brazil

Evapotranspiration is the process of water loss of vegetated soil due to evaporation and transpiration, and it may be estimated by various empirical methods. This study had the objective to carry out the evaluation of the performance of the following methods: Blaney-Criddle, Jensen-Haise, Linacre, Solar Radiation, Hargreaves-Samani, Makkink, Thornthwaite, Camargo, Priestley-Taylor and Original Penman in the estimation of the potential evapotranspiration when compared to the Penman-Monteith standard method (FAO56) to the climatic conditions of Uberaba, state of Minas Gerais, Brazil. A set of 21 years monthly data (1990 to 2010) was used, working with the climatic elements: temperature, relative humidity, wind speed and insolation. The empirical methods to estimate reference evapotranspiration were compared with the standard method using linear regression, simple statistical analysis, Willmott agreement index (d) and performance index (c). The methods Makkink and Camargo showed the best performance, with "c" values ​​of 0.75 and 0.66, respectively. The Hargreaves-Samani method presented a better linear relation with the standard method, with a correlation coefficient (r) of 0.88.

Impact of the substitution of reference annual streamflow by monthly streamflow on the potential use of water resources

The consideration of the streamflow seasonality has a high potential to improve the water use. In order to give subsidies to the optimization of water use, it was evaluated the impact of the change of reference annual streamflow by the monthly streamflows in the potential water use throughout the hydrography of Paracatu sub-Basin. It was evaluated the impact on Q7,10 (lowest average streamflow during a 7-day period with an average recurrence of 10 years) and on Q95 (permanent flow present 95% of the time). The use of monthly streamflow to substitute the annual streamflow had a high potential of improvement of water resources use in the sub-Basin studied. The use of monthly Q 7,10 in substitution of annual Q 7,10 increases the potential water use that vary from about 10% in the months of lower water availability to values exceeding 200% in the months with higher availability of surface water resources. The use of monthly Q95 in substitution of the annual Q95 implies in changes oscillating from reduction of 37% in months of higher water restriction to values exceeding 100% in the months of higher availability, so the use of monthly Q95 instead of the annual Q95 enables the more rational and safe use of water resources.

Estimation methods of reference evapotranspiration (ETo) for Uberlândia -MG

One approach to verify the adequacy of estimation methods of reference evapotranspiration is the comparison with the Penman-Monteith method, recommended by the United Nations of Food and Agriculture Organization - FAO, as the standard method for estimating ET0. This study aimed to compare methods for estimating ET0, Makkink (MK), Hargreaves (HG) and Solar Radiation (RS), with Penman-Monteith (PM). For this purpose, we used daily data of global solar radiation, air temperature, relative humidity and wind speed for the year 2010, obtained through the automatic meteorological station, with latitude 18° 91' 66" S, longitude 48° 25' 05" W and altitude of 869m, at the National Institute of Meteorology situated in the Campus of Federal University of Uberlandia - MG, Brazil. Analysis of results for the period were carried out in daily basis, using regression analysis and considering the linear model y = ax, where the dependent variable was the method of Penman-Monteith and the independent, the estimation of ET0 by evaluated methods. Methodology was used to check the influence of standard deviation of daily ET0 in comparison of methods. The evaluation indicated that methods of Solar Radiation and Penman-Monteith cannot be compared, yet the method of Hargreaves indicates the most efficient adjustment to estimate ETo.

Evolution in the profile of thyroid cancer cases treated in an oncology reference service: what changed in the last 20 years

Objective: To evaluate the characteristics of thyroid carcinoma cases treated at a reference hospital for cancer between 2008 and 2010.Methods: we studied 807 cases and analyzed the following clinicopathologic variables: symptoms, risk factors, diagnostic tests, staging, histological type, treatment performed and complications.Results: Females were more affected, with 660 cases (82%). The average age at diagnosis was 44.5 years. Prior exposure to ionizing radiation was reported by 22 (3%) patients, a family history of thyroid cancer by 89 (11%), and 289 (36%) individuals reported other types of cancer in the family. The fine needle aspiration biopsy was the main parameter for surgical indication and was suggestive of carcinoma in 463 patients (57%). Papillary carcinoma was the most common histological type, with 780 cases (96.6%). There were 728 (90%) total thyroidectomies, 43 (5.3%) reoperations or partial thyroidectomies followed by totalization, 23 (2.8%) extended thyroidectomies and only 13 (1.6%) partial thyroidectomies (lobectomy with isthmectomy). Neck dissection associated with thyroidectomy was done in 158 patients (19.5%). We observed a predominance of tumors classified as T1 in 602 (74.6%) patients. Transient hypocalcemia was the most frequent complication.Conclusion: The results show that the worldwide increase in the incidence of thyroid cancer has changed the profile of patients seen at a referral service. In addition, there were changes in the type of surgical treatment used, with increased use of total thyroidectomy in relation to partial and subtotal ones, and decreased use of elective neck dissections.

Epidemiological profile and postoperative complications of women undergoing gynecological surgery in a reference center in the northern brazilian legal amazon

Objective: To evaluate the epidemiological profile and the operative complications of patients undergoing gynecological operations for benign diseases in a tertiary public hospital in the state of Roraima, Brazil. Methods: We conducted a retrospective survey through the analysis of 518 records of patients submitted to gynecological operations between January and June 2012. We included the three major operations during this period (n = 175): hysterectomy, colpoperineoplasty and suburethral sling placement. We excluded 236 cases of tubal ligation and 25 cases where it was not possible to access to medical records. Results: The mean age was 47.6 years; the education level of most patients was completed junior high (36.6%); 77% were from the State capital, 47.4% were in stable relationships and 26.3% were housewives. The majority of patients had given birth three or more times (86.6%), with previous vaginal delivery in 50.2%, and cesarean delivery, 21%. The main diagnostic indications for surgical treatment were uterine myoma (46.3%), urinary incontinence (27.4%) and genital dystopias (17.7%). We found three cases (1.7%) of high-grade intraepithelial lesions on Pap smear. The most common procedure was total hysterectomy (19.8%), 15.5% vaginally. The most common complication was wound infection (2.2%). Conclusion: Women undergoing gynecological operations due to benign disease had a mean age of 47 years, most had levels of basic education, came from the capital, were in stable relationships, predominantly housewives, multiparous and showed low operative complication rates.

Assessment of pelvic floor by three-dimensional-ultrasound in primiparous women according to delivery mode: initial experience from a single reference service in Brazil

PURPOSE: To evaluate changes to the pelvic floor of primiparous women with different delivery modes, using three-dimensional ultrasound. METHODS: A prospective cross-sectional study on 35 primiparae divided into groups according to the delivery mode: elective cesarean delivery (n=10), vaginal delivery (n=16), and forceps delivery (n=9). Three-dimensional ultrasound on the pelvic floor was performed on the second postpartum day with the patient in a resting position. A convex volumetric transducer (RAB4-8L) was used, in contact with the large labia, with the patient in the gynecological position. Biometric measurements of the urogenital hiatus were taken in the axial plane on images in the rendering mode, in order to assess the area, anteroposterior and transverse diameters, average thickness, and avulsion of the levator ani muscle. Differences between groups were evaluated by determining the mean differences and their respective 95% confidence intervals. The proportions of levator ani muscle avulsion were compared between elective cesarean section and vaginal birth using Fisher's exact test. RESULTS: The mean areas of the urogenital hiatus in the cases of vaginal and forceps deliveries were 17.0 and 20.1 cm², respectively, versus 12.4 cm² in the Control Group (elective cesarean). Avulsion of the levator ani muscle was observed in women who underwent vaginal delivery (3/25), however there was no statistically significant difference between cesarean section and vaginal delivery groups (p=0.5). CONCLUSION: Transperineal three-dimensional ultrasound was useful for assessing the pelvic floor of primiparous women, by allowing pelvic morphological changes to be differentiated according to the delivery mode.