Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

Thirty-seven patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR) was achieved, defined as: a) presence of less than 5% blasts in the bone marrow, with b) white blood cells >103/mm3, c) platelets >105/mm3 and d) hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7%) patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days), was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS) were observed in 7 (19%), 6 (16%) and 4 (11%) patients, respectively. Thirteen (35%) patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3) and six of these presented with new signs of coagulopathy after chemotherapy. Four (11%) patients died secondarily to intracerebral hemorrhage (IH) and two (5.4%) dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity). RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

The hematopoietic stroma

All blood cells are derived from a small common pool of totipotent cells, called hematopoietic stem cells. The process is strictly regulated by the hematopoietic microenvironment, which includes stromal cells, extracellular matrix molecules and soluble regulatory factors. Several experimental in vitro assays have been developed for the study of hematopoietic differentiation, and have provided valuable information on the stroma, which includes, among other cell types, macrophages, fibroblasts, adipocytes, and endothelial cells. The composition, ontogeny, and function in physiological as well as pathological conditions of stroma are discussed.

Siirtohinnoittelun kehittäminen etäluettavilta mittareilta saatavan datan avulla sähkönjakeluyhtiö Mäntsälän Sähkö Oy:lle

Sähkönsiirtomaksuilla katetaan luonnollisena alueellisena monopolina toimivan paikallisen sähkönjakeluyhtiön toiminta. Koska sähköverkkoyhtiöt toimivat monopoliasemassa, niiden toimintaa valvoo Energiavirasto. Energiavirasto valvoo pääasiassa verkkoyhtiöiden liikevaihtoa ja toiminnan tehokkuutta. Verkkoyhtiöiden toimintaa säätää Suomessa sähkömarkkinalaki. Verkkoyhtiöiden kustannusrakenne on hyvin sidottu verkoston kustannuksiin. Koska sähköverkoston kustannukset ovat pitkän käyttöiän ja suurien alkuinvestointien vuoksi vuosittain kiinteät ja merkittävän suuret, olisi verkkoyhtiön kannalta tärkeää, että vuosittaiset tulot eivät suuresti vaihtelisi. Nykyisellä hinnoittelumallilla kuitenkin verkkoyhtiöiden tulot jäävät hyvin riippuvaisiksi talven kylmyydestä. Nykyisin Suomessa yleisesti käytettävässä siirtohinnoittelun hinnoittelumallissa ei huomioida myöskään sitä, että verkkoyhtiön kustannukset ovat enemmän riippuvaisia verkossa siirretyistä tehoista kuin energioista. Siirtohinnoittelun kannalta on tapahtunut ja on tapahtumassa merkittäviä muutoksia. Etäluettavien sähkönkulutusmittarien käyttöönoton myötä asiakkaiden kulutuksesta saadaan huomattavasti entistä enemmän tietoa, mikä auttaa kustannusvastaavien hintojen määrittämisessä. Samaan aikaan asiakkaiden sähkön käyttö voi muuttua huomattavasti varsinkin sähköautojen ja lämpöpumppujen yleistymisen myötä. Tämän työn tarkoituksena on luoda Mäntsälän Sähkö Oy:lle sähkönsiirtohinnoittelun kustannuksia vastaavien hintojen määrittämiseksi laskentasovellus sekä selvittää tulevaisuuden siirtohinnoittelun toteuttamismahdollisuuksia. Lyhyen aikavälin suunnittelussa keskitytään kustannusvastaavien hintojen määrittämiseen keskihintaperiaatteen avulla ja pidemmän aikavälin suunnittelussa asiakkaiden huipputehoihin perustuvan hinnoittelun toteuttamisen vaikutuksiin sekä verkkoyhtiön että asiakkaan näkökulmasta.

Proteinase activity regulation by glycosaminoglycans

There are few reports concerning the biological role and the mechanisms of interaction between proteinases and carbohydrates other than those involved in clotting. It has been shown that the interplay of enzymes and glycosaminoglycans is able to modulate the activity of different proteases and also to affect their structures. From the large number of proteases belonging to the well-known protease families and also the variety of carbohydrates described as widely distributed, only few events have been analyzed more deeply. The term "family" is used to describe a group of proteases in which every member shows an evolutionary relationship to at least one other protease. This relationship may be evident throughout the entire sequence, or at least in that part of the sequence responsible for catalytic activity. The majority of proteases belong to the serine, cysteine, aspartic or metalloprotease families. By considering the existing limited proteolysis process, in addition to the initial idea that the proteinases participate only in digestive processes, it is possible to conclude that the function of the enzymes is strictly limited to the cleavage of intended substrates since the destruction of functional proteins would result in normal tissue damage. In addition, the location as well as the eventual regulation of protease activity promoted by glycosaminoglycans can play an essential role in the development of several physiopathological conditions.

Behavioristinen investointitutkimus ja investointilaskentamenetelmien opetus Suomessa

Tämän Pro gradu -tutkielman tavoitteena on selvittää, millaisia menetelmiä Suomen kauppatieteellisissä yksiköissä opetetaan laskentatoimen opiskelijoille investointien kannattavuuden arvioimiseen, ja onko sillä havaittavaa vaikutusta yritysten tosiasialliseen investointikäyttäytymiseen pitkällä aikavälillä. Tutkimusmuotona käytetään laadullista tutkimusmenetelmää. Tutkimuksen teoriaosuudessa esitellään kirjallisuuskatsaus behavioristiseen investointi-tutkimukseen ja empiirinen aineisto puolestaan kerättiin kyselytutkimuksella, jonka kohderyhmänä oli suomalaisissa kauppakorkeakouluissa toimivat laskentatoimen professorit. Tutkimusaineistoa myös syvennettiin puolistrukturoidulla haastattelulla. Tutkimustulosten perusteella havaitaan, että nettonykyarvon käyttö suomalaisissa yrityksissä on lähentynyt kansainvälistä tasoa, mutta reaalioptioiden käyttö on miltei olematonta verrattuna kansainvälisiin käytäntöihin. Suomessa syvällisimmin opetetut investointilaskentamenetelmät ovat nettonykyarvon ja sisäisen korkokannan menetelmät. Tuloksista voidaan päätellä myös, että klassiset investointilaskentamenetelmät, bisnesanalytiikka ja reaalioptiot ovat tärkeä osa laskentatoimen opetusta tulevaisuudessa, mutta syvällisesti reaalioptioihin fokusoitunutta opetusta ei juurikaan ole tällä hetkellä tarjolla.

Expression and characterization of an N-truncated form of the NifA protein of Azospirillum brasilense

Azospirillum brasilense is a nitrogen-fixing bacterium associated with important agricultural crops such as rice, wheat and maize. The expression of genes responsible for nitrogen fixation (nif genes) in this bacterium is dependent on the transcriptional activator NifA. This protein contains three structural domains: the N-terminal domain is responsible for the negative control by fixed nitrogen; the central domain interacts with the RNA polymerase σ54 co-factor and the C-terminal domain is involved in DNA binding. The central and C-terminal domains are linked by the interdomain linker (IDL). A conserved four-cysteine motif encompassing the end of the central domain and the IDL is probably involved in the oxygen-sensitivity of NifA. In the present study, we have expressed, purified and characterized an N-truncated form of A. brasilense NifA. The protein expression was carried out in Escherichia coli and the N-truncated NifA protein was purified by chromatography using an affinity metal-chelating resin followed by a heparin-bound resin. Protein homogeneity was determined by densitometric analysis. The N-truncated protein activated in vivo nifH::lacZ transcription regardless of fixed nitrogen concentration (absence or presence of 20 mM NH4Cl) but only under low oxygen levels. On the other hand, the aerobically purified N-truncated NifA protein bound to the nifB promoter, as demonstrated by an electrophoretic mobility shift assay, implying that DNA-binding activity is not strictly controlled by oxygen levels. Our data show that, while the N-truncated NifA is inactive in vivo under aerobic conditions, it still retains DNA-binding activity, suggesting that the oxidized form of NifA bound to DNA is not competent to activate transcription.

Effect of point mutations on Herbaspirillum seropedicae NifA activity

NifA is the transcriptional activator of the nif genes in Proteobacteria. It is usually regulated by nitrogen and oxygen, allowing biological nitrogen fixation to occur under appropriate conditions. NifA proteins have a typical three-domain structure, including a regulatory N-terminal GAF domain, which is involved in control by fixed nitrogen and not strictly required for activity, a catalytic AAA+ central domain, which catalyzes open complex formation, and a C-terminal domain involved in DNA-binding. In Herbaspirillum seropedicae, a β-proteobacterium capable of colonizing Graminae of agricultural importance, NifA regulation by ammonium involves its N-terminal GAF domain and the signal transduction protein GlnK. When the GAF domain is removed, the protein can still activate nif genes transcription; however, ammonium regulation is lost. In this work, we generated eight constructs resulting in point mutations in H. seropedicae NifA and analyzed their effect on nifH transcription in Escherichia coli and H. seropedicae. Mutations K22V, T160E, M161V, L172R, and A215D resulted in inactive proteins. Mutations Q216I and S220I produced partially active proteins with activity control similar to wild-type NifA. However, mutation G25E, located in the GAF domain, resulted in an active protein that did not require GlnK for activity and was partially sensitive to ammonium. This suggested that G25E may affect the negative interaction between the N-terminal GAF domain and the catalytic central domain under high ammonium concentrations, thus rendering the protein constitutively active, or that G25E could lead to a conformational change comparable with that when GlnK interacts with the GAF domain.

Antioxidant activity of rosemary and oregano ethanol extracts in soybean oil under thermal oxidation

Four experiments were conducted to measure the antioxidant activity of ethanol extracts of rosemary and oregano compared with synthetic antioxidants such as TBHQ and BHA/BHT. The antioxidant activity was determined and results differed from those of the Oven test at 63º C. Peroxide values and absorptivities at 232 nm of soybean oil under Oven test were lower in treatments with 25, 50, 75, 100 and 200 mg.Kg-1 TBHQ than in treatments with 1000 mg.Kg-1 oregano extract (O), 500 mg.Kg-1 rosemary extract (R) and their mixture R+O. All the treatments were effective in controlling the thermal oxidation of oils; the natural extracts were as effective as BHA+BHT and less effective than TBHQ. The natural extracts were mixed with 25, 50, 75 and 100 mg.Kg-1 TBHQ and then added to the oil. No improvement in antioxidative properties was observed. The best antioxidant concentration could be determined from polynomial regression and quadratic equation from the experimental data.

Shirshovin lause PI-algebroissa

Tässä työssä esitetään venäläisen matemaatikon A.I. Shirshovin teorioita ja tuloksia sanojen kombinatoriikasta. Lisäksi näytetään miten ne soveltuvat PI-algebrojen maailmaan. Shirshovin tuloksia tarkasteltaessa käsitellään sanoja erillisinä kombinatorisina objekteina ja todistetaan Shirshovin Lemma, joka on tämän työn perusta. Lemmanmukaan tarpeeksi pitkille sanoille saadaan tiettyä säännönmukaisuutta ja se todistetaan kolme kertaa. Ensimmäisestä saadaan tarpeeksi pitkän sanan olemassaolo.Toinen todistus mukailee Shirshovin alkuperäistä todistusta. Kolmannessa todistuksessa annetaan tarpeeksi pitkälle sanalle paremmin käytäntöön soveltuva raja. Tämän jälkeen käsitellään sanoja algebrallisina objekteina. Työn päätuloksena todistetaan Shirshovin Korkeuslause, jonka mukaan jokainen äärellisesti generoidunPI-algebran alkio on sanojen ω1k1 ···ωdkd lineaarikombinaatio, missä sanojen ωi pi-tuudet sekä indeksi i ovat rajatut. Shirshovin Korkeuslauseesta seuraa suoraan positiivinen ratkaisu Kurochin ongelmaan PI-algebroilla sekä saadaan raja alkioiden lukumäärälle, jolla algebra generoituu moduliksi. Lisäksi esitetään toisena sovelluksena ilman todistuksia Shirshovin soveltuvuus Jacobsonin radikaalin nilpotenttisuuteen. Pääsääntöisenä lähteenä käytetään A. Kanel-Belowin ja L. H. Rowenin kirjaa: Computational aspects of polynomial identities.

Rheological and thermophysical properties of blackberry juice

Rheological and thermophysical properties were determined for blackberry juice, which was produced from blackberry fruit at 9.1 ± 0.5 °Brix and density of 1.0334 ± 0.0043 g cm-3. The concentration process was performed using a roto evaporator, under vacuum, to obtain concentrated juice at about 60 °Brix. In order to obtain different concentrations, concentrated juice was diluted with distilled water. Rheological measurements were carried out using a Rheotest 2.1 Searle type rheometer. In the tested ranges, the samples behaved as pseudoplastic fluids, and the Power-Law model was satisfactorily fitted to the experimental data. The friction factor was measured for blackberry juice in laminar flow conditions of pseudoplastic behavior. Thermal conductivity, thermal diffusivity and density of blackberry juice at 9.4 to 58.4 °Brix were determined, in triplicate, at 0.5 to 80.8 °C. Polynomial regression was performed to fit experimental data obtaining a good fit. Both temperature and concentration showed a strong influence on thermophysical properties of blackberry juice. Calculated apparent specific heat values varied from 2.416 to 4.300 kJ.kg-1 °C in the studied interval.

Defining Contexts in Context-Free Grammars

This thesis introduces an extension of Chomsky’s context-free grammars equipped with operators for referring to left and right contexts of strings.The new model is called grammar with contexts. The semantics of these grammars are given in two equivalent ways — by language equations and by logical deduction, where a grammar is understood as a logic for the recursive definition of syntax. The motivation for grammars with contexts comes from an extensive example that completely defines the syntax and static semantics of a simple typed programming language. Grammars with contexts maintain most important practical properties of context-free grammars, including a variant of the Chomsky normal form. For grammars with one-sided contexts (that is, either left or right), there is a cubic-time tabular parsing algorithm, applicable to an arbitrary grammar. The time complexity of this algorithm can be improved to quadratic,provided that the grammar is unambiguous, that is, it only allows one parsefor every string it defines. A tabular parsing algorithm for grammars withtwo-sided contexts has fourth power time complexity. For these grammarsthere is a recognition algorithm that uses a linear amount of space. For certain subclasses of grammars with contexts there are low-degree polynomial parsing algorithms. One of them is an extension of the classical recursive descent for context-free grammars; the version for grammars with contexts still works in linear time like its prototype. Another algorithm, with time complexity varying from linear to cubic depending on the particular grammar, adapts deterministic LR parsing to the new model. If all context operators in a grammar define regular languages, then such a grammar can be transformed to an equivalent grammar without context operators at all. This allows one to represent the syntax of languages in a more succinct way by utilizing context specifications. Linear grammars with contexts turned out to be non-trivial already over a one-letter alphabet. This fact leads to some undecidability results for this family of grammars

A statistical approach to define some tofu processing conditions

The aim of this work was to make tofu from soybean cultivar BRS 267 under different processing conditions in order to evaluate the influence of each treatment on the product quality. A fractional factorial 2(5-1) design was used, in which independent variables (thermal treatment, coagulant concentration, coagulation time, curd cutting, and draining time) were tested at two different levels. The response variables studied were hardness, yield, total solids, and protein content of tofu. Polynomial models were generated for each response. To obtain tofu with desirable characteristics (hardness ~4 N, yield 306 g tofu.100 g-1 soybeans, 12 g proteins.100 g-1 tofu and 22 g solids.100 g-1 tofu), the following processing conditions were selected: heating until boiling plus 10 minutes in water bath, 2% dihydrated CaSO4 w/w, 10 minutes coagulation, curd cutting, and 30 minutes draining time.

Optimization of the extraction of carrageenan from Kappaphycus alvarezii using response surface methodology

This study aims to optimize an alternative method of extraction of carrageenan without previous alkaline treatment and ethanol precipitation using Response Surface Methodology (RSM). In order to introduce an innovation in the isolation step, atomization drying was used reducing the time for obtaining dry carrageenan powder. The effects of extraction time and temperature on yield, gel strength, and viscosity were evaluated. Furthermore, the extracted material was submitted to structural analysis, by infrared spectroscopy and nuclear magnetic resonance spectroscopy (¹H-NMR), and chemical composition analysis. Results showed that the generated regression models adequately explained the data variation. Carrageenan yield and gel viscosity were influenced only by the extraction temperature. However, gel strength was influenced by both, extraction time and extraction temperature. Optimal extraction conditions were 74 ºC and 4 hours. In these conditions, the carrageenan extract properties determined by the polynomial model were 31.17%, 158.27 g.cm-2, and 29.5 cP for yield, gel strength, and viscosity, respectively, while under the experimental conditions they were 35.8 ± 4.68%, 112.50 ± 4.96 g.cm-2, and 16.01 ± 1.03 cP, respectively. The chemical composition, nuclear magnetic resonance spectroscopy, and infrared spectroscopy analyses showed that the crude carrageenan extracted is composed mainly of κ-carrageenan.

Optimization and functionality of millet supplemented pasta

Abstract Millets are having superior nutritional qualities and health benefits; hence they can be used for supplementation of pasta. Pasta was prepared using composite flour (CF) of durum wheat semolina (96%) and carrot pomace (4%) supplemented with finger millet flour (FMF, 0-20g), pearl millet flour (PMF, 0-30g) and carboxy methyl cellulose (CMC, 2-4g). Second order polynomial described the effect of FMF, PMF and CMC on lightness, firmness, gruel loss and overall acceptability of extruded pasta products. Results indicate that an increasing proportion of finger and pearl millet flour had signed (p≤0.05) negative effect on lightness, firmness, gruel loss and overall acceptability. However, CMC addition showed significant (p≤0. 05) positive effect on firmness, overall acceptability and negative effect on gruel loss of cooked pasta samples. Numeric optimization results showed that optimum values for extruded pasta were 20g FMF, 12g PMF and 4g CMC per 100g of CF and 34ml water with 0.981 desirability. The pasta developed is nutritionally rich as it contains protein (10.16g), fat (6g), dietary fiber (16.71g), calcium (4.23mg), iron (3.99mg) and zinc (1.682mg) per 100g.

Modeling and kinetic study of bio-ethanol production from soy protein concentrate by-product

Abstract The aim of this work was to evaluate a non-agitated process of bioethanol production from soybean molasses and the kinetic parameters of fermentation using a strain of Saccharomyces cerevisiae (ATCC® 2345). Kinetic experiment was conducted in medium with 30% (w v-1) of soluble solids without supplementation or pH adjustment. The maximum ethanol concentration was in 44 hours, the ethanol productivity was 0.946 g L-1 h-1, the yield over total initial sugars (Y1) was 47.87%, over consumed sugars (Y2) was 88.08% and specific cells production rate was 0.006 h-1. The mathematical polynomial was adjusted to the experimental data and provided very similar parameters of yield and productivity. Based in this study, for one ton of soybean molasses can be produced 103 kg of anhydrous bioethanol.