The Roman Republican Navy : from the sixth century to 167 BC

Työ käsittelee Rooman laivaston kehitystä, toimintaa ja osallistumista laajenemispolitiikkaan, jossa Rooma kasvoi kaupunkivaltiosta Välimeren hallitsijaksi. Rooma on aikaisemmissa tutkimuksissa nähty maavaltiona vailla kiinnostusta merenkulkuun. On katsottu, että ainoa merkittävä merisota Rooman historiassa on ensimmäinen puunilaissota (264-241 eKr.) ja että siinäkin roomalaiset (jotka historioitsija Polybius kuvaa vasta-alkajiksi) menestyivät Karthagoa vastaan turvautumalla laskusiltoihin, joiden avulla he saattoivat muuttaa meritaistelun maataisteluksi. Polybiuksen kuvaukseen on aina tähän asti luotettu. On katsottu että Roomalla ei ollut laivastoa ennen ensimmäistä puunilaissotaa ja että Rooma kaikissa sodissaan panosti merisodankäyntiin mahdollisimman vähän. Tämä työ pyrkii kumoamaan nämä käsitykset. Laivasto oli osallisena ja ehdottoman välttämätön kaikissa Rooman laajenemispolitiikan käänteissä. Arkeologian tiedot osoittavat, että ennen ensimmäistä puunilaissotaa Rooma kehittyi ja siitä tuli merkittävä kaupunki nimenomaan kaupankäynnin ja ulkomaisten kontaktien seurauksena. Se ei siis ollut puhdas agraarivaltio. Roomalaisilla oli laivasto jo viimeistään 500-luvulta lähtien eKr. ja sitä käytettiin Rooman laajentaessa valtaansa Italiassa. Näin ollen ensimmäisessä puunilaissodassa läntisen Välimeren herruudesta kilpaili kaksi merivaltiota, Rooma ja Karthago. Toinen puunilaissota (218-201) tunnetaan yleensä Hannibalin tulosta Alppien yli Italiaan, mutta se oli myöskin merkittävä merisota ja karthagolaiset hävisivät sen nimenomaan merellä. Rooma osallistui kilpailuun itäisen Välimeren hallinnasta ja kukisti Makedonian ja Syyrian laivastot, jotka eivät olleet mitenkään Rooman laivaston veroisia. Kaikista Rooman vastustajista Karthagolla olisi ollut suurin mahdollisuus pysäyttää Rooman laivaston voittokulu toisessa puunilaissodassa. Laivastoa käytettiin moniin eri tarkoituksiin. Suuret meritaistelut eivät ole ainoa osoitus laivastojen mukanaolosta ja merkityksestä, vaan on myös otettava huomion sotalaivojen rakenne ja toimintaedellytykset. Sotalaivat oli rakennettu taisteluita varten ja niissä oli hyvin niukasti säilytystilaa. Niiden oli päästävä laskemaan maihin aina kun miehistö tarvitsi vettä, ruokaa ja lepoa. Laivastot saattoivat toimia vain niiden rannikoiden tuntumassa, joiden satamiin ja laskupaikkoihin niillä oli turvallinen pääsy. Roomalaiset olivat hyvin tietoisia tästä. Suuret merentakaiset sotaretket Afrikkaan, Espanjaan, Kreikkaan ja Vähän-Aasian rannikolle perustuivat kaikki siihen, että Rooman laivasto hallitsi purjehdusreittejä ja sopivia laskupaikkoja ja saattoi huolehtia joukkojen ja varusteiden kuljettamisesta kaukana taisteleville armeijoille. Samalla Rooman laivasto kävi itsenäistä sotaa merellä ja haastoi ja kukisti kaikki Välimeren merivaltiot. 130-luvulle eKr. tultaessa se oli lyönyt vihollisensa ja riisunut aseista liittolaisensa; Rooman laivasto hallitsi Välimerta yksin.

Valinnan vapautta kulttuurin kehyksissä : Saviastian valmistusprosessi ja sen muutos Rääkkylän Vihin kampakeraamisen ajan asuinpaikalla

Tutkimuksessa kuvaillaan Rääkkylän Vihi 1:n kampakeraamisen ajan asuinpaikan saviastia-aineistossa havaittavaa vaihtelua ja pohditaan vaihtelun syitä. Astioissa havaittavan vaihtelun katsotaan syntyneen valmistajien valmistusprosessin aikana teke¬mistä valinnoista. Työssä selvitetään, millaisia vaihtoehtoisia tapoja valmistusvaiheiden toteuttamisessa on ollut ja mikä valmistajan tekemiä valintoja on ohjannut. Tulkintaa aineistosta syvennetään etsimällä muuttujien välistä yhteisvaihtelua ja tarkastelemalla astioiden ominaisuuksien yhteyttä polton tulokseen, käytöstä kertoviin jälkiin, korjaukseen ja astioiden levintään. Tutkimusaineistona ovat 130 Vihin asuinpaikan keramiikka-aineistosta määriteltyä astiaa. Käsitys saviastian valmistajan tiedossa olleista ja käyttämistä vaihtoehdoista luotiin teknisten valintojen attribuuttianalyysilla. Koristelun luokittelussa käytettiin apuna tilastollisia moni¬muuttujamenetelmiä (ryhmittely- ja erotteluanalyysi, moniulotteinen skaalaus). Levintää analysoitiin aineistosta erotetun neljän levintätyypin avulla. Astioiden ominaisuuksissa esiintyvä vaihtelu osoittaa astian valmistajilla olleen useita vaihtoehtoisia tapoja toteuttaa jokainen val¬mistusvaihe. Tästä huolimatta on havaittavissa toistuvia yhteyksiä koristelun, sekoitteen, seinämän paksuuden, reunan muodon ja astian levinnän välillä. Talkkisekoitteisten astioiden seinämät ovat ohuemmat ja kyljen koristelu yksinkertaisempaa kuin hiekka- tai murskasekoitteisten astioiden. Talkkisekoitteisten astioiden polton tulos on parempi ja niitä on korjattu harvemmin kuin hiekka- tai murskasekoitteisia astioita. Erisekoitteisten astioiden välillä on eroa myös reunan muodossa. Astioiden levintään pohjautuvan suhteellisen kronologian perusteella erilaisia sekoitteita, koristelutapoja ja reunatyyppejä on käytetty rinnan suurimman osaa asuinpaikan käytön ajasta. Astioiden ominaisuuksissa kuitenkin tapahtuu muutoksia asuinpaikan käytön aikana: seinämät ohenevat, tasapaksu ja tasainen reuna sekä yksinkertaisempi koristelutapa yleistyvät ja talkinkäyttö sekoitteena lisääntyy. Tutkimustulokset tukevat siten tuoreimman tutkimuksen tuloksia kampakeraamisissa aineistoissa esiintyvästä samanaikaisesta vaihtelusta, joka on suurempaa kuin perinteisessä Aarne Äyräpään typologis-kronologisessa mallissa esitetään. Työssä pohditaan erilaisia selitysvaihtoehtoja astian valmistajien valintoihin ja niissä ja siten valmistusprosessissa tapahtuviin muutoksiin, mutta täsmällisiä syitä niihin ei vielä voida antaa.

Dynamics of contour, object and face processing in the human visual cortex

The neural basis of visual perception can be understood only when the sequence of cortical activity underlying successful recognition is known. The early steps in this processing chain, from retina to the primary visual cortex, are highly local, and the perception of more complex shapes requires integration of the local information. In Study I of this thesis, the progression from local to global visual analysis was assessed by recording cortical magnetoencephalographic (MEG) responses to arrays of elements that either did or did not form global contours. The results demonstrated two spatially and temporally distinct stages of processing: The first, emerging 70 ms after stimulus onset around the calcarine sulcus, was sensitive to local features only, whereas the second, starting at 130 ms across the occipital and posterior parietal cortices, reflected the global configuration. To explore the links between cortical activity and visual recognition, Studies II III presented subjects with recognition tasks of varying levels of difficulty. The occipito-temporal responses from 150 ms onwards were closely linked to recognition performance, in contrast to the 100-ms mid-occipital responses. The averaged responses increased gradually as a function of recognition performance, and further analysis (Study III) showed the single response strengths to be graded as well. Study IV addressed the attention dependence of the different processing stages: Occipito-temporal responses peaking around 150 ms depended on the content of the visual field (faces vs. houses), whereas the later and more sustained activity was strongly modulated by the observers attention. Hemodynamic responses paralleled the pattern of the more sustained electrophysiological responses. Study V assessed the temporal processing capacity of the human object recognition system. Above sufficient luminance, contrast and size of the object, the processing speed was not limited by such low-level factors. Taken together, these studies demonstrate several distinct stages in the cortical activation sequence underlying the object recognition chain, reflecting the level of feature integration, difficulty of recognition, and direction of attention.

The Interplay Between KSHV-encoded Viral Cyclin and CDK-inhibitors p27Kip1 and p21Cip1 -implications for Viral Lymphomagenesis

Cell division, which leads to the birth of two daughter cells, is essential for the growth and development of all organisms. The reproduction occurs in a series of events separated in time, designated as the cell cycle. The cell cycle progression is controlled by the activity of cyclin-dependent kinases (CDK). CDKs pair with cyclins to become catalytically active and phosphorylate a broad range of substrates required for cell cycle progression. In addition to cyclins, CDKs are regulated by inhibitory and activating phosphorylation events, binding to CDK-inhibitory proteins (CKI), and also by subcellular localization. The control of the CDK activity is crucial in preventing unscheduled progression of the cell cycle with mistakes having potentially hazardous consequences, such as uncontrolled proliferation of the cells, a hallmark of cancer. The mammalian cell cycle is a target of several DNA tumor viruses that can deregulate the host s cell cycle with their viral oncoproteins. A human herpesvirus called Kaposi s sarcoma herpesvirus (KSHV) is implicated in the cause of Kaposi s sarcoma (KS) and lymphoproliferative diseases such as primary effusion lymphomas (PEL). KSHV has pirated several cell cycle regulatory genes that it uses to manipulate its host cell and to induce proliferation. Among these gene products is a cellular cyclin D homologue, called viral cyclin (v-cyclin) that can activate cellular CDKs leading to the phosphorylation of multiple target proteins. Intriguingly, PELs that are naturally infected with KSHV consistently express high levels of CDK inhibitor protein p27Kip1 and still proliferate actively. The aim of this study was to investigate v-cyclin complexes and their activity in PELs, and search for an explanation why CKIs, such as p27Kip1 and p21Cip1 are unable to inhibit cell proliferation in this type of lymphoma. In this study, we found that v-cyclin binds to p27Kip1 in PELs, and confirmed this novel interaction also in the overexpression models. We observed that p27Kip1 associated with v-cyclin was also phosphorylated by a v-cyclin-associated kinase and identified cellular CDK6 as the major kinase partner of v-cyclin responsible for this phosphorylation. Analysis of the p27Kip1 residues targeted by v-cyclin-CDK6 revealed that serine 10 (S10) is the major phosphorylation site during the latent phase of the KSHV replication cycle. This phosphorylation led to the relocalization of p27Kip1 to the cytoplasm, where it is unable to inhibit nuclear cyclin-CDK complexes. In the lytic phase of the viral replication cycle, the preferred phosphorylation site on p27Kip1 by v-cyclin-CDK6 changed to threonine 187 (T187). T187 phosphorylation has been shown to lead to ubiquitin-mediated degradation of p27Kip1 and downregulation of p27Kip1 was also observed here. v-cyclin was detected also in complex with p21Cip1, both in overexpression models and in PELs. Phosphorylation of p21Cip1 on serine 130 (S130) site by v-cyclin-CDK6 functionally inactivated p21Cip1 and led to the circumvention of G1 arrest induced by p21Cip1. Moreover, p21Cip1 phosphorylated by v-cyclin-associated kinase showed reduced binding to CDK2, which provides a plausible explanation why p21Cip1 is unable to inhibit cell cycle progression upon v-cyclin expression. Our findings clarify the mechanisms on how v-cyclin evades the inhibition of cell cycle inhibitors and suggests an explanation to the uncontrolled proliferation of KSHV-infected cells.

Routine Measurement of Health-Related Quality of Life in Assessing Cost-Effectiveness in Secondary Health Care

Aims: The aims of this study were 1) to identify and describe health economic studies that have used quality-adjusted life years (QALYs) based on actual measurements of patients' health-related quality of life (HRQoL); 2) to test the feasibility of routine collection of health-related quality of life (HRQoL) data as an indicator of effectiveness of secondary health care; and 3) to establish and compare the cost-utility of three large-volume surgical procedures in a real-world setting in the Helsinki University Central Hospital, a large referral hospital providing secondary and tertiary health-care services for a population of approximately 1.4 million. Patients and methods: So as to identify studies that have used QALYs as an outcome measure, a systematic search of the literature was performed using the Medline, Embase, CINAHL, SCI and Cochrane Library electronic databases. Initial screening of the identified articles involved two reviewers independently reading the abstracts; the full-text articles were also evaluated independently by two reviewers, with a third reviewer used in cases where the two reviewers could not agree a consensus on which articles should be included. The feasibility of routinely evaluating the cost-effectiveness of secondary health care was tested by setting up a system for collecting HRQoL data on approximately 4 900 patients' HRQoL before and after operative treatments performed in the hospital. The HRQoL data used as an indicator of treatment effectiveness was combined with diagnostic and financial indicators routinely collected in the hospital. To compare the cost-effectiveness of three surgical interventions, 712 patients admitted for routine operative treatment completed the 15D HRQoL questionnaire before and also 3-12 months after the operation. QALYs were calculated using the obtained utility data and expected remaining life years of the patients. Direct hospital costs were obtained from the clinical patient administration database of the hospital and a cost-utility analysis was performed from the perspective of the provider of secondary health care services. Main results: The systematic review (Study I) showed that although QALYs gained are considered an important measure of the effectiveness of health care, the number of studies in which QALYs are based on actual measurements of patients' HRQoL is still fairly limited. Of the reviewed full-text articles, only 70 reported QALYs based on actual before after measurements using a valid HRQoL instrument. Collection of simple cost-effectiveness data in secondary health care is feasible and could easily be expanded and performed on a routine basis (Study II). It allows meaningful comparisons between various treatments and provides a means for allocating limited health care resources. The cost per QALY gained was 2 770 for cervical operations and 1 740 for lumbar operations. In cases where surgery was delayed the cost per QALY was doubled (Study III). The cost per QALY ranges between subgroups in cataract surgery (Study IV). The cost per QALY gained was 5 130 for patients having both eyes operated on and 8 210 for patients with only one eye operated on during the 6-month follow-up. In patients whose first eye had been operated on previous to the study period, the mean HRQoL deteriorated after surgery, thus precluding the establishment of the cost per QALY. In arthroplasty patients (Study V) the mean cost per QALY gained in a one-year period was 6 710 for primary hip replacement, 52 270 for revision hip replacement, and 14 000 for primary knee replacement. Conclusions: Although the importance of cost-utility analyses has during recent years been stressed, there are only a limited number of studies in which the evaluation is based on patients own assessment of the treatment effectiveness. Most of the cost-effectiveness and cost-utility analyses are based on modeling that employs expert opinion regarding the outcome of treatment, not on patient-derived assessments. Routine collection of effectiveness information from patients entering treatment in secondary health care turned out to be easy enough and did not, for instance, require additional personnel on the wards in which the study was executed. The mean patient response rate was more than 70 %, suggesting that patients were happy to participate and appreciated the fact that the hospital showed an interest in their well-being even after the actual treatment episode had ended. Spinal surgery leads to a statistically significant and clinically important improvement in HRQoL. The cost per QALY gained was reasonable, at less than half of that observed for instance for hip replacement surgery. However, prolonged waiting for an operation approximately doubled the cost per QALY gained from the surgical intervention. The mean utility gain following routine cataract surgery in a real world setting was relatively small and confined mostly to patients who had had both eyes operated on. The cost of cataract surgery per QALY gained was higher than previously reported and was associated with considerable degree of uncertainty. Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is two-fold compared to hip replacement. Cost-utility results from the three studied specialties showed that there is great variation in the cost-utility of surgical interventions performed in a real-world setting even when only common, widely accepted interventions are considered. However, the cost per QALY of all the studied interventions, except for revision hip arthroplasty, was well below 50 000, this figure being sometimes cited in the literature as a threshold level for the cost-effectiveness of an intervention. Based on the present study it may be concluded that routine evaluation of the cost-utility of secondary health care is feasible and produces information essential for a rational and balanced allocation of scarce health care resources.

Molecular Genetic Background of Tumours in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a hereditary tumour predisposition syndrome. Its phenotype includes benign cutaneous and uterine leiomyomas (CLM, ULM) with high penetrance and rarer renal cell cancer (RCC), most commonly of papillary type 2 subtype. Over 130 HLRCC families have been identified world-wide but the RCC phenotype seems to concentrate in families from Finland and North America for unknown reasons. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. FH encodes the enzyme fumarase from mitochondrial citric acid cycle. Fumarase enzyme activity or type or site of the FH mutation are unassociated with disease phenotype. The strongest evidence for tumourigenesis mechanism in HLRCC supports a hypoxia inducible factor driven process called pseudohypoxia resulting from accumulation of the fumarase substrate fumarate. In this study, to assess the importance of gene- or exon-level deletions or amplifications of FH in patients with HLRCC-associated phenotypes, multiplex ligation-dependent probe amplification (MLPA) method was used. One novel FH mutation, deletion of exon 1, was found in a Swedish male patient with an evident HLRCC phenotype with CLM, RCC, and a family history of ULM and RCC. Six other patients with CLM and 12 patients with only RCC or uterine leiomyosarcoma (ULMS) remained FH mutation-negative. These results suggest that copy number aberrations of FH or its exons are an infrequent cause of HLRCC and that only co-occurrence of benign tumour types justifies FH-mutation screening in RCC or ULMS patients. Determination of the genomic profile of 11 HLRCC-associated RCCs from Finnish patients was performed by array comparative genomic hybridization. The most common copy number aberrations were gains of 2, 7, and 17 and losses of 13q12.3-q21.1, 14, 18, and X. When compared to aberrations of sporadic papillary RCCs, HLRCC-associated RCCs harboured a distinct DNA copy number profile and lacked many of the changes characterizing the sporadic RCCs. The findings suggest a divergent molecular pathway for tumourigenesis of papillary RCCs in HLRCC. In order to find a genetic modifier of RCC risk in HLRCC, genome-wide linkage and identical by descent (IBD) analysis studies were performed in Finnish HLRCC families with microsatellite marker mapping and SNP-array platforms. The linkage analysis identified only one locus of interest, the FH gene locus in 1q43, but no mutations were found in the genes of the region. IBD analysis yielded no convincing haplotypes shared by RCC patients. Although these results do not exclude the existence of a genetic modifier for RCC risk in HLRCC, they emphasize the role of FH mutations in the malignant tumourigenesis of HLRCC. To study the benign tumours in HLRCC, genome-wide DNA copy number and gene expression profiles of sporadic and HLRCC ULMs were defined with modern SNP- and gene-expression array platforms. The gene expression array suggests novel genes involved in FH-deficient ULM tumourigenesis and novel genes with putative roles in propagation of sporadic ULM. Both the gene expression and copy number profiles of HLRCC ULMs differed from those of sporadic ULMs indicating distinct molecular basis of the FH-deficient HLRCC tumours.

From a tree to a stand in Finnish boreal forests: biomass estimation and comparison of methods

There is an increasing need to compare the results obtained with different methods of estimation of tree biomass in order to reduce the uncertainty in the assessment of forest biomass carbon. In this study, tree biomass was investigated in a 30-year-old Scots pine (Pinus sylvestris) (Young-Stand) and a 130-year-old mixed Norway spruce (Picea abies)-Scots pine stand (Mature-Stand) located in southern Finland (61º50' N, 24º22' E). In particular, a comparison of the results of different estimation methods was conducted to assess the reliability and suitability of their applications. For the trees in Mature-Stand, annual stem biomass increment fluctuated following a sigmoid equation, and the fitting curves reached a maximum level (from about 1 kg/yr for understorey spruce to 7 kg/yr for dominant pine) when the trees were 100 years old. Tree biomass was estimated to be about 70 Mg/ha in Young-Stand and about 220 Mg/ha in Mature-Stand. In the region (58.00-62.13 ºN, 14-34 ºE, ≤ 300 m a.s.l.) surrounding the study stands, the tree biomass accumulation in Norway spruce and Scots pine stands followed a sigmoid equation with stand age, with a maximum of 230 Mg/ha at the age of 140 years. In Mature-Stand, lichen biomass on the trees was 1.63 Mg/ha with more than half of the biomass occurring on dead branches, and the standing crop of litter lichen on the ground was about 0.09 Mg/ha. There were substantial differences among the results estimated by different methods in the stands. These results imply that a possible estimation error should be taken into account when calculating tree biomass in a stand with an indirect approach.