Minimization of biosynthetic costs in adaptive gene expression responses of yeast to environmental changes

Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

Painless Indirect Argon Laser in High Risk Proliferative Diabetic Retinopathy.

Background: Proliferative retinopathy is an important cause of vision loss in diabetic patients. Incomplete panretinal photocoagulation (PRP) can lead to recurrent proliferation of new vessels. Patients and Methods: We retrospectively analysed the outcome of patients with high risk proliferative diabetic retinopathy (PDR) previously treated with slit lamp PRP who underwent indirect fill in argon laser treatment with scleral indentation under anesthesia for persistent neovascular proliferation. Results: Seventeen eyes of ten patients were included. The mean age at diabetes onset was 17.3 years SD 16.2 (range 2-44). All patients reported long standing poor glycemic control (mean HbA1c: 8.5 % SD 1.3 range 5.9-10.2). The area of retinal ischemia decreased significantly from 15 ± 7.5 disk areas (DA) before fill-in laser to 3.2 ± 4.2 DA after fill-in laser (p = 0.001). The new vessels also regressed significantly after laser treatment 8.6 ± 6.1 DA before treatment versus 6.5 ± 6.4 DA after laser treatment, (p = 0.044). Quiescent PDR was reached in 10 eyes (58.8 %) at the last visit. Conclusions: Fill-in indirect argon laser under general anesthesia should be considered to achieve further new vessels regression in high risk PDR patients. Scleral indentation and absence of pain may allow for more extensive laser application.

Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds.

Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

Production costs and fruit yield profitability in the initial harvest of custard apple trees

The aim of this study was to estimate the production cost and economic indicators associated with the production and sales of fruits from 20 custard apple progenies during the initial five harvests, in order to identify the harvest season from which custard apple exploitation becomes profitable, as well as the most promising progenies from an economic point of view. The fruit yield data upon which the present work was based were obtained during the period from 2001 to 2005, in an experiment that evaluated 20 custard apple half-sibling progenies, under sprinkler irrigation. The progenies were evaluated in a random block design with five replicates and plots consisting of four plants each. The exploitation of custard apple progenies only showed to be a profitable agribusiness after the fourth year. Before that, only A3 and A4 progenies in the second year, and P3 and P11 in the third year provided profitable incomes. Considering the methodological assumptions imposed concerning the time period analysis and the prices as of July 2007, the most important profitability indicators (operating profit, return index and equilibrium price) evidenced that the A4 progeny is the most recommended, although other progenies are also highlighted, such as FJ1 and FJ2. As already discussed, the progenies showing the highest average yields of five harvests are not always the most economically recommendable ones.

Modelling additional costs caused by a new product feature

Työn tavoitteena oli mallintaa uuden tuoteominaisuuden aiheuttamat lisäkustannukset ja suunnitella päätöksenteon työkalu Timberjack Oy:n kuormatraktorivalmistuksen johtoryhmälle. Tarkoituksena oli luoda karkean tason malli, joka sopisi eri tyyppisten tuoteominaisuuksien kustannuksien selvittämiseen. Uuden tuoteominaisuuden vaikutusta yrityksen eri toimintoihin selvitettiin haastatteluin. Haastattelukierroksen tukena käytettiin kysymyslomaketta. Haastattelujen tavoitteena oli selvittää prosessit, toiminnot ja resurssit, jotka ovat välttämättömiä uuden tuoteominaisuuden tuotantoon saattamisessa ja tuotannossa. Malli suunniteltiin haastattelujen ja tietojärjestelmästä hankitun tiedon pohjalta. Mallin rungon muodostivat ne prosessit ja toiminnot, joihin uudella tuoteominaisuudella on vaikutusta. Huomioon otettiin sellaiset resurssit, joita uusi tuoteominaisuus kuluttaa joko välittömästi, tai välillisesti. Tarkasteluun sisällytettiin ainoastaan lisäkustannukset. Uuden tuoteominaisuuden toteuttamisesta riippumattomat, joka tapauksessa toteutuvat yleiskustannukset jätettiin huomioimatta. Malli on yleistys uuden tuoteominaisuuden aiheuttamista lisäkustannuksista, koska tarkoituksena on, että se sopii eri tyyppisten tuoteominaisuuksien aiheuttamien kustannusten selvittämiseen. Lisäksi malli soveltuu muiden pienehköjen tuotemuutosten kustannusten kartoittamiseen.

Paineilmajärjestelmän optimoinnin hyödyt tehtaan tuotantoprosessissa

Paineilmaa käytetään teollisuudessa hyvin yleisesti. Teollistuneissa maissa teollisuuden käyttämästä energiasta 8-10 % kuluu paineilman tuottamiseen. Paineilmakompressoreiden nykyaikaisen ohjausjärjestelmän avulla voidaan säästää paineilmajärjestelmän energiakustannuksia jopa 30 %. Ohjauksen optimoinnin yhteydessä on havaittu epäkohtia joiden poistaminen on parantanut tuotantolaitosten toimintaan niin, että saadut säästöt ovat olleet jopa energiasäästöjä suuremmat. Näitä optimoinnin välillisiä hyötyjä haluttiin selvittää tarkemmin. Tutkimuksessa perehdyttiin paineilman käytön ongelmiin eri tuotantolaitoksissa ja arvioitiin paineilmajärjestelmän optimoinnin vaikutuksia tehtaiden tuotantoon. Koska paineilmaa käytetään monissa tehtaiden kriittisissä kohteissa, on tutkimuskohteiden paineilmajärjestelmän ongelmista aiheutunut merkittäviä tuotannonmenetyksiä ja lisäkustannuksia. Merkittävimmät paperitehtaiden tuotantoa vaikeuttavat paineilmajärjestelmän tekniset ongelmat liittyvät paineilman puhtausvaatimuksiin ja riittävän verkkopaineen ylläpidon vaikeuteen. Organisatorisia ongelmia ovat paineilmajärjestelmän käyttöhenkilöstön asiantuntemuksen puutteellisuudet. Näistä aiheutuvaa tuotannon epäluotettavuutta voidaan merkittävästi pienentää kehittämällä paineilmakompressoreita, jälkikäsittelyä, ohjausta ja valvontaa alan asiantuntijoiden avustuksella.

Transfer pricing tool development process based on valve package production costs

Tämän diplomityön päätavoitteena oli parantaa kehitetyn kustannusperusteisen siirtohinnoittelutyökalun ominaisuuksia osastokohtaisen kustannusarviointiprosessin käyttöön. Työ on vaikeutunut lähimenneisyyden heikosta hintakyselyiden vastauskyvystä. Työn pääongelmana oli kerätä luotettavaa tuotannonohjausjärjestelmän kustannusaineistoa osittain vanhentuneista vakioventtiilien koneistus- ja materiaalitiedosta. Tutkimuksessa käytetyt tärkeimmät tutkimusmenetelmät voidaan jakaa siirtohinnoittelu- ja kustannusarvioprosessien kirjallisuustutkimukseen, kenttäanalyysiin ja nykyisen Microsoft Excel –siirtohinnoittelutyökalun kehittämiseen eri osastojen rajapinnassa. Siirtohinnoittelumenetelmät ovat yleisesti jaettu kustannus-, markkina- ja neuvotteluperusteisiin malleihin, jotka harvoin sellaisenaan kohtaavat siirtohinnoittelulle asetetut tavoitteet. Tämä ratkaisutapa voi johtaa tilanteisiin, jossa kaksi erillistä menetelmää sulautuvat yhteen. Lisäksi varsinaiseen siirtohinnoittelujärjestelmään yleensä vaikuttavat useat sisäiset ja ulkoiset tekijät. Lopullinen siirtohinnoittelumenetelmä tulisi ehdottomasti tukea myös yrityksen visiota ja muita liiketoiminnalle asetettuja strategioita. Työn tuloksena saatiin laajennettu Microsoft Excel –sovellus, joka vaatii sekä vuosittaista että kuukausittaista erikoisventtiilimateriaalien hinta- ja toimitusaikatietojen päivittämistä. Tämä ratkaisutapa ehdottomasti parantaa kustannusarviointiprosessia, koska myös alihankkijatietoja joudutaan tutkimaan systemaattisesti. Tämän jälkeen koko siirtohinnoitteluprosessia voidaan kehittää muuntamalla kokoonpano- ja testaustyövaiheiden kustannusrakennetta toimintoperustaisen kustannuslaskentamallin mukaiseksi.

Impact on costs of a case management intervention for emergency department frequent users

Background: In most of the emergency departments (ED) in developed countries, a subset of patients visits the ED frequently. Despite their small numbers, these patients are the source of a disproportionally high number of all ED visits, and use a significant proportion of healthcare resources. They place a heavy economic burden on hospital and healthcare system budgets overall. In order to improve the management of these patients, the University hospital of Lausanne, Switzerland implemented a case management intervention (CM) between May 2012 and July 2013. In this randomized controlled trial, 250 frequent ED users (visits>5 during previous 12 months) were allocated to either the CM group or the standard ED care (SC) group and followed up for 12 months. The first result of the CM was to reduce significantly the ED visits. The present study examined whether the CM intervention also reduced the costs generated by the ED frequent users not only from the hospital perspective, but also from the healthcare system perspective. Methods: Cost data were obtained from the hospital's analytical accounting system and from health insurances. Multivariate linear models including a fixed effect "group" and socio-demographic characteristics and health-related variables were run.

Paying the costs of reproduction.

When a female fly mates it produces a hormone that increases the size of its midgut and enhances fat metabolism in order to provide the energy needed for reproduction.

Recovery Risk and Labor Costs in Public-Private Partnerships : Contractual Choice in the US Water industry

We use an ordered logistic model to empirically examine the factors that explain varying degrees of private involvement in the U.S. water sector through public-private partnerships. Our estimates suggest that a variety of factors help explain greater private participation in this sector. We find that the risk to private participants regarding cost recovery is an important driver of private participation. The relative cost of labor is also a key factor in determining the degree of private involvement in the contract choice. When public wages are high relative to private wages, private participation is viewed as a source of cost savings. We thus find two main drivers of greater private involvement: one encouraging private participation by reducing risk, and another encouraging government to seek out private participation in lowering costs.

Privatization, cooperation and costs of solid waste services in small towns

This paper analyzes the cost implications of privatization and cooperation in the provision of solid waste services for a sample of small municipalities. In conducting this empirical analysis, a survey is first designed and administered to municipalities in the Spanish region of Aragon, and then an estimation of the determinants of service costs is undertaken, considering the possible endogeneity of delivery choices. Our findings indicate that cooperation is more effective than privatization in saving costs. Both production forms can enable small municipalities to cut costs by exploiting scale economies. However, the fact that inter-municipal cooperation involves lower transaction costs and is less likely to be affected by competition problems would seem to account for the fact that it is a more effective way of reducing costs.

Comparison of electricity generation costs

The economical competitiveness of various power plant alternatives is compared. The comparison comprises merely electricity producing power plants. Combined heat and power (CHP) producing power will cover part of the future power deficit in Finland, but also condensing power plants for base load production will be needed. The following types of power plants are studied: nuclear power plant, combined cycle gas turbine plant, coal-fired condensing power plant, peat-fired condensing power plant, wood-fired condensing power plant and wind power plant. The calculations are carried out by using the annuity method with a real interest rate of 5 % per annum and with a fixed price level as of January 2008. With the annual peak load utilization time of 8000 hours (corresponding to a load factor of 91,3 %) the production costs would be for nuclear electricity 35,0 €/MWh, for gas based electricity 59,2 €/MWh and for coal based electricity 64,4 €/MWh, when using a price of 23 €/tonCO2 for the carbon dioxide emission trading. Without emission trading the production cost of gas electricity is 51,2 €/MWh and that of coal electricity 45,7 €/MWh and nuclear remains the same (35,0 €/MWh) In order to study the impact of changes in the input data, a sensitivity analysis has been carried out. It reveals that the advantage of the nuclear power is quite clear. E.g. the nuclear electricity is rather insensitive to the changes of nuclear fuel price, whereas for natural gas alternative the rising trend of gas price causes the greatest risk. Furthermore, increase of emission trading price improves the competitiveness of the nuclear alternative. The competitiveness and payback of the nuclear power investment is studied also as such by using various electricity market prices for determining the revenues generated by the investment. The profitability of the investment is excellent, if the market price of electricity is 50 €/MWh or more.