Olla elävän sanat : Roolirunon laji Maila Pylkkösen teoksessa Arvo. Vanhaäiti puhuu runonsa

Maila Pylkkönen (1931 1986) was one of the most important modernist poets in Finland and a central figure in developing the dramatic monologue in Finnish literature. The study examines Pylkkönen s poetic work Arvo. Vanhaäiti puhuu runonsa (Value. An old woman speaks her poem, 1959) as an example of the dramatic monologue, approaching it from three perspectives: its generic features and background, and the poetic framework to which it connects in the context of Pylkkönen s poetry. In addition to methods of literary scholarship, the poetic analysis benefits from a linguistic approach. The study shows that the dramatic monologue genre drives Pylkkönen s first work, Klassilliset tunteet (Classical feelings, 1957), in a context of finding poetic identity, characterised by the expression to be the words of a living creature . The study demonstrates that important generic features of the dramatic monologue, namely, a poem representing a speech-event and a hierarchical structure, are also Arvo s most significant generic features. Arvo s poems as speech-events are examined for their internal progressive, pragmatic unity constructed through single line units; for their function as narratives dealing with the life story of an old woman, Arvo s speaker; and from the perspective of the communication between the old woman and the poems other characters. Arvo s speech-events can also be seen as semantic shifts from one poem to another: the poems construct semantic stages representing different phases of the old woman s life. The study demonstrates that analysis of Arvo s hierarchical structure, that is, the relationship between the speaker and the rhetorical levels, reveals the work s structural and ideological wholeness by focusing on the old woman s emotions: longing, loneliness and alienation from the world. In other words, the contradictions between the explicit level of the speaker and an implied rhetorical level open up the tragedy of an old woman s daily life. Study of Arvo s hierarchical structure also highlights the special position of the reader in the framework of a dramatic monologue. The elements of a dramatic present in which the old woman s emotions are conveyed, an italicized opening poem, and the work s title Value invite the reader to consider Arvo as a structural and ideological whole. The function of Arvo s hierarchical structure is to ask the reader to recognise the hopelessness of the old woman s situation, understand it, and even identify with it.

Memory disorders in acute encephalitis : A neuropsychological study

Acute encephalitis is an inflammation of the brain, mostly caused by viral infection. A variety of cognitive symptoms may persist after the acute stage, and neuropsychological assessment is crucial in evaluation of the outcome. The most commonly reported sequelae are memory deficits. The main aims of this study were to investigate the types of memory impairment in various encephalitides, the frequency of global amnesia following encephalitis, and the changes in the deficits during follow-up. Between 1 January 1985 and 31 December 1994, 77 adult patients under the age of 75 with acute encephalitis but without alcohol abuse, or coexisting or previous neurological diseases were consecutively referred for neuropsychological examination at the Department of Neurology, Helsinki University Central Hospital. The aetiology was established in 44/77 (57%) patients; 17 had Herpes simplex virus encephalitis (HSVE). Transient amnesia (TENA) at the acute stage of the disease was found in 70% of patients. Furthermore, similarly to brain trauma, TENA was found to indicate cognitive outcome. The frequency of persisting global amnesia syndrome with both anterograde and retrograde amnesia in all encephalitic patients was 6%. One patient had isolated retrograde amnesia, which is very rare. In HSVE the frequency of global amnesia was 12.5%, which is lower than expected. As a group, HSVE patients were not found to have a homogeneous pattern of amnesia, instead subgroups among all encephalitic patients were observed: some patients had impaired semantic memory, some had difficulty predominantly with executive functions and some suffered from an increased forgetting rate. Herpes zoster encephalitis was found to result in mild memory impairment only, and the qualitative features indicated a subcortical dysfunction. On the whole, the cognitive deficits were predominantly found to diminish during follow-up. Progressive deterioration was often associated with intractable epilepsy. The frequency of dementia was 12.5%. In conclusion, the neuropsychological outcome, especially in HSVE, was more favourable than has previously been reported, possibly due to early acyclovir medication. Memory disorders after encephalitis should not be considered uniform, and the need for neuropsychological rehabilitation should be considered case-by-case

Oscillatory brain activity in memory disorders

Neuronal oscillations are thought to underlie interactions between distinct brain regions required for normal memory functioning. This study aimed at elucidating the neuronal basis of memory abnormalities in neurodegenerative disorders. Magnetoencephalography (MEG) was used to measure oscillatory brain signals in patients with Alzheimer s disease (AD), a neurodegenerative disease causing progressive cognitive decline, and mild cognitive impairment (MCI), a disorder characterized by mild but clinically significant complaints of memory loss without apparent impairment in other cognitive domains. Furthermore, to help interpret our AD/MCI results and to develop more powerful oscillatory MEG paradigms for clinical memory studies, oscillatory neuronal activity underlying declarative memory, the function which is afflicted first in both AD and MCI, was investigated in a group of healthy subjects. An increased temporal-lobe contribution coinciding with parieto-occipital deficits in oscillatory activity was observed in AD patients: sources in the 6 12.5 Hz range were significantly stronger in the parieto-occipital and significantly weaker in the right temporal region in AD patients, as compared to MCI patients and healthy elderly subjects. Further, the auditory steady-state response, thought to represent both evoked and induced activity, was enhanced in AD patients, as compared to controls, possibly reflecting decreased inhibition in auditory processing and deficits in adaptation to repetitive stimulation with low relevance. Finally, the methodological study revealed that successful declarative encoding and retrieval is associated with increases in occipital gamma and right hemisphere theta power in healthy unmedicated subjects. This result suggests that investigation of neuronal oscillations during cognitive performance could potentially be used to investigate declarative memory deficits in AD patients. Taken together, the present results provide an insight on the role of brain oscillatory activity in memory function and memory disorders.

Bovine mucopolysaccharidosis type IIIB

Mucopolysaccharidosis IIIB, an autosomal recessive lysosomal storage disorder of heparan sulfate caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene, was recently discovered in cattle. Clinical signs include progressive ataxia, stumbling gait, swaying and difficulty in balance and walking. These clinical signs are usually first observed at approximately 2 years of age and then develop progressively over the lifespan of the animals. Affected bulls were found to be homozygous for the missense mutation E452K (c.1354G>A). The availability of mutational analysis permits screening for the NAGLU mutation to eradicate this mutation from the cattle breeding population.

Harmonising GAP programs for fresh produce in ASEAN region

Many forces are driving the global demand for assurance that fruit and vegetables are safe to eat and of the right quality, and are produced and handled in a manner that does not cause harm to the environment and the health, safety and welfare of workers. The impact of these driving forces is that retailer requirements for suppliers to comply with Good Agricultural Practice (GAP) is increasing and governments are strengthening legal requirements for food safety, environmental protection, and worker health, safety and welfare. The implementation of GAP programs currently within the ASEAN (Association of South East Asian Nations) region varies, with some countries having government certified systems and others beginning the journey with awareness programs for farmers. Under a project funded by the ASEAN Australia Development Cooperation Program, a standard for ASEAN GAP has been developed to harmonise GAP Programs in the region. The goal is to facilitate trade between ASEAN countries and to global markets, improve viability for farmers, and help sustain a safe food supply and the environment. ASEAN GAP is an umbrella standard that individual member countries will benchmark their national programs against to gain equivalence. The scope of ASEAN GAP covers the production, harvesting and postharvest handling of fresh fruit and vegetables on farm and postharvest handling in locations where produce is packed for sale. ASEAN GAP consists of four modules covering food safety, environmental management, worker health, safety and welfare, and produce quality. Each module can be used alone or in combination with other modules. This enables progressive implementation of ASEAN GAP, module by module based on individual country priorities.

Next Generation SHRM Research: From Covariation to Causation

[Excerpt] In response to the longstanding and repeated criticisms that HR does not add value to organizations, the past 10 years has seen a burgeoning of research attempting to demonstrate that progressive HR practices result in higher organizational performance. Huselid’s (1995)groundbreaking study demonstrated that a set of HR practices he referred to as High Performance Work Systems (HPWS) were related to accounting profits and market value of firms. Since then, a number of studies have shown similar positive relationships between HR practices and various measures of firm performance. While the studies comprising what I refer to as “first generation SHRM research” have added to what is becoming a more convincing body of evidence of the positive relationship between HR and performance, this body tends to lack sufficient data to demonstrate that the relationship is actually causal in the sense that HR practices, when instituted, lead to higher performance. This next generation of SHRM research will begin (and, in fact has begun) to focus on designing more rigorous tests of the hypothesis that employing progressive HRM systems actually results in higher organizational performance. This generation of research will focus on two aspects: demonstrating the HRM value chain, and proving causality as opposed to merely covariation.

Collaborative Design in a Virtual Learning Environment : Three Design Experiments in Textile Teacher Education

The aim of the study was to analyze and facilitate collaborative design in a virtual learning environment (VLE). Discussions of virtual design in design education have typically focused on technological or communication issues, not on pedagogical issues. Yet in order to facilitate collaborative design, it is also necessary to address the pedagogical issues related to the virtual design process. In this study, the progressive inquiry model of collaborative designing was used to give a structural level of facilitation to students working in the VLE. According to this model, all aspects of inquiry, such as creating the design context, constructing a design idea, evaluating the idea, and searching for new information, can be shared in a design community. The study consists of three design projects: 1) designing clothes for premature babies, 2) designing conference bags for an international conference, and 3) designing tactile books for visually impaired children. These design projects constituted a continuum of design experiments, each of which highlighted certain perspectives on collaborative designing. The design experiments were organized so that the participants worked in design teams, both face-to-face and virtually. The first design experiment focused on peer collaboration among textile teacher students in the VLE. The second design experiment took into consideration end-users needs by using a participatory design approach. The third design experiment intensified computer-supported collaboration between students and domain experts. The virtual learning environments, in these design experiments, were designed to support knowledge-building pedagogy and progressive inquiry learning. These environments enabled a detailed recording of all computer-mediated interactions and data related to virtual designing. The data analysis was based on qualitative content analysis of design statements in the VLE. This study indicated four crucial issues concerning collaborative design in the VLE in craft and design education. Firstly, using the collaborative design process in craft and design education gives rise to special challenges of building learning communities, creating appropriate design tasks for them, and providing tools for collaborative activities. Secondly, the progressive inquiry model of collaborative designing can be used as a scaffold support for design thinking and for reflection on the design process. Thirdly, participation and distributed expertise can be facilitated by considering the key stakeholders who are related to the design task or design context, and getting them to participate in virtual designing. Fourthly, in the collaborative design process, it is important that team members create and improve visual and technical ideas together, not just agree or disagree about proposed ideas. Therefore, viewing the VLE as a medium for collaborative construction of the design objects appears crucial in order to understand and facilitate the complex processes in collaborative designing.

The impact of dry matter, ripeness and internal defects on consumer perceptions of avocado quality and intentions to purchase.

Insights into the relative importance of various aspects of product quality can be provided through quantitative analysis of consumer preference and choice of fruit. In this study, methods previously used to establish taste preferences for kiwifruit (Harker et al., 2008) and conjoint approaches were used to determine the influence of three key aspects of avocado quality on consumer liking and willingness to purchase fruit: dry matter percentage (DM), level of ripeness (firmness) and internal defects (bruising). One hundred and seven consumers tasted avocados with a range of DM levels from ~20% (minimally mature) to nearly 40% (very mature), and at a range of fruit firmness (ripeness) stages (firm-ripe to soft-ripe). Responses to bruising, a common quality defect in fruit obtained from the retail shelf, were examined using a conjoint approach in which consumers were presented with photographs showing fruit affected by damage of varying severity. In terms of DM, consumers showed a progressive increase in liking and intent to buy avocados as the DM increased. In terms of ripeness, liking and purchase intent was higher in avocados that had softened to a firmness of 6.5 N or below (hand-rating 5). For internal defects, conjoint analysis revealed that price, level of bruising and incidence of bruising all significantly lowered consumers' future purchase decision, but the latter two factors had a greater impact than price. These results indicate the usefulness of the methodology, and also provide realistic targets for Hass avocado quality on the retail shelf.

Virtuaalimaailmoja valtaamassa : verkko-opetusinnovaation leviäminen koulun maantieteeseen vuosituhannen vaihteessa

Tutkimus käsittelee verkko-opetusinnovaation leviämistä perusasteen ja lukion maantieteeseen vuosina 1998–2004. Työssä sovellettiin opetusinnovaation leviämismallia ja innovaatioiden diffuusioteoriaa. Aineisto hankittiin seitsemänä vuotena kyselylomakkeilla maantieteen verkko-opetuksen edelläkävijäopettajilta, jotka palauttivat 326 lomaketta. Tutkimuksen pääongelmat olivat 1) Millaisia edellytyksiä edelläkävijäopettajilla on käyttää verkko-opetusta koulun maantieteessä? 2) Mitä sovelluksia ja millä tavoin edelläkävijäopettajat käyttävät maantieteen verkko-opetuksessa? 3) Millaisia käyttökokemuksia edelläkävijäopettajat ovat saaneet maantieteen verkko-opetuksesta? Tutkimuksessa havaittiin, että tietokoneiden riittämätön määrä ja puuttuminen aineluokasta vaikeuttivat maantieteen verkko-opetusta. Työssä kehitettiin opettajien digitaalisten mediataitojen kuutiomalli, johon kuuluvat tekniset taidot, informaation prosessointitaidot ja viestintätaidot. Opettajissa erotettiin kolme verkko-opetuksen käyttäjätyyppiä: informaatiohakuiset kevytkäyttäjät, viestintähakuiset peruskäyttäjät ja yhteistyöhakuiset tehokäyttäjät. Verkko-opetukseen liittyi intensiivisiä myönteisiä ja kielteisiä kokemuksia. Se toi iloa ja motivaatiota opiskeluun. Sitä pidettiin rikastuttavana lisänä, joka haluttiin integroida opetukseen hallitusti. Edelläkävijäopettajat ottivat käyttöön tietoverkoissa olevaa informaatiota ja sovelsivat työvälineohjelmia. He pääsivät alkuun todellisuutta jäljittelevien virtuaalimaailmojen: satelliittikuvien toistaman maapallon, digitaalikarttojen ja simulaatioiden käytössä. Opettajat kokeilivat verkon sosiaalisia tiloja reaaliaikaisen viestinnän, keskusteluryhmien ja ryhmätyöohjelmien avulla. Mielikuvitukseen perustuvat virtuaalimaailmat jäivät vähälle sillä opettajat eivät juuri pelanneet viihdepelejä. He omaksuivat virtuaalimaailmoista satunnaisia palasia käytettävissä olevan laite- ja ohjelmavarustuksen mukaan. Virtuaalimaailmojen valtaus eteni tutkimuksen aikana digitaalisen informaation hyödyntämisestä viestintäsovelluksiin ja aloittelevaan yhteistyöhön. Näin opettajat laajensivat virtuaalireviiriään tietoverkkojen dynaamisiksi toimijoiksi ja pääsivät uusin keinoin tyydyttämään ihmisen universaalia tarvetta yhteyteen muiden kanssa. Samalla opettajat valtautuivat informaation kuluttajista sen tuottajiksi, objekteista subjekteiksi. Verkko-opetus avaa koulun maantieteelle huomattavia mahdollisuuksia. Mobiililaitteiden avulla informaatiota voidaan kerätä ja tallentaa maasto-olosuhteissa, ohjelmilla sitä voidaan muuntaa muodosta toiseen. Internetin autenttiset ja ajantasaiset materiaalit tuovat opiskeluun konkretiaa ja kiinnostavuutta, mallit, simulaatiot ja paikkatieto havainnollistavat ilmiöitä. Viestintä- ja yhteistyövälineet sekä sosiaaliset informaatiotilat vahvistavat yhteistyötä. Avainsanat: verkko-opetus, internet, virtuaalimaailmat, maantiede, innovaatiot

Verkkokurssilla : Opiskelijoiden kokemuksia toiminnasta yhteisöllisessä oppimisprosessissa Fle2-ympäristössä ja kokemusten näkyminen toimintaan osallistumisessa

The study examines one case of students' experiences from the activity in a collaborative learning process in a networked learning environment, and explores whether or not the experiences explain the participation or lack of participation in the activities. As a research task the students' experiences in the database of the networked learning environment, participating in its construction, and the ways of working needed to build the database, were examined. To contrast the students' experiences, their actual participation in the building of the database was clarified. Based on actual participation, groups more active and more passive than average were separated, and their experiences were compared to each other. The research material was collected from the course Cognitive and Creative Processes, which was offered to studentsof the Department of Textile Teacher Education in University of Helsinki, and students of the Departments of Teacher Education Units giving textile education in Turku, Rauma and Savonlinna in the beginning of 2001. In this course, creativity was examined from a psychological and sosiocultural context with the aim of realizing a collaborative progressive inquiry process. The course was held in a network-based Future Learning Environment (Fle 2) except for the starting lecture and training the use of the learning environment. This study analyzed the learning diaries that the students had sent to the tutor once a week for four weeks, and the final thoughts written into the database of the learning environment. Content analysis was applied as the research method. The case was enriched from another point of view by examining the messages the students had written into the learning environment with the social network analysis. The theoretical base of the study looks at the research of computer-supported collaborative learning, the conceptions of learning as a process of participation and knowledge building, and the possibilities and limitations of network-based learning environments. The research results show, that both using the network-based learning environment and collaborative ways of studying were new to the students. The students were positively surprised by the feedback and support provided by the community. On the other hand, they also experienced problems with facelessness and managing the information in the learning environment. The active students seemed to be more ready for a progressive inquiry process. It can be seen from their attitudes and actions that they have strived to participate actively and invested into the process both from their own and the community's point of view. The more passive students reported their actions to get credits and they had a harder time of perceiving the thoughts presented in the net as common progression. When arranging similar courses in the future, attention should be paid to how to get the students to act in ways necessary for knowledge building, and different from more traditional ways of studying. The difficulties of students used to traditional studying methods to adapt to collaborative knowledge building were evident on the course Cognitive and Creative Processes. Keywords: computer supported collaborative learning, knowledge building, progressive Inquiry, participation

Myelodysplasia as a cause of hindlimb ataxia in two beef calves.

Myelodysplasia is a general term referring to abnormal development of the spinal cord. Unless associated with vertebral malformations, it can be difficult to distinguish clinically from other causes of spinal cord disease. These case reports describe the clinical and pathological findings in two calves with a distinctive non-progressive pelvic limb ataxia. The syndrome was observed in two calves on a large, extensively managed beef cattle property near Richmond, north Queensland. Both calves had similar clinical signs, including hindlimb ataxia with swaying of the pelvis and a well-coordinated bilateral hopping-like action. The differential diagnoses are discussed. A focal or diffuse myelodysplasia should be suspected in calves that have exhibited a non-progressive hindlimb ataxia from birth.

The effect of data sources and quality on the predictive capacity of CLIMEX models: an assessment of Teleonemia scrupulosa and Octotoma scabripennis for the biocontrol of Lantana camara in Australia

Understanding the effects of different types and quality of data on bioclimatic modeling predictions is vital to ascertaining the value of existing models, and to improving future models. Bioclimatic models were constructed using the CLIMEX program, using different data types – seasonal dynamics, geographic (overseas) distribution, and a combination of the two – for two biological control agents for the major weed Lantana camara L. in Australia. The models for one agent, Teleonemia scrupulosa Stål (Hemiptera:Tingidae) were based on a higher quality and quantity of data than the models for the other agent, Octotoma scabripennis Guérin-Méneville (Coleoptera: Chrysomelidae). Predictions of the geographic distribution for Australia showed that T. scrupulosa models exhibited greater accuracy with a progressive improvement from seasonal dynamics data, to the model based on overseas distribution, and finally the model combining the two data types. In contrast, O. scabripennis models were of low accuracy, and showed no clear trends across the various model types. These case studies demonstrate the importance of high quality data for developing models, and of supplementing distributional data with species seasonal dynamics data wherever possible. Seasonal dynamics data allows the modeller to focus on the species response to climatic trends, while distributional data enables easier fitting of stress parameters by restricting the species envelope to the described distribution. It is apparent that CLIMEX models based on low quality seasonal dynamics data, together with a small quantity of distributional data, are of minimal value in predicting the spatial extent of species distribution.

Measuring the effects of mergers and acquisitions on the economic performance of real estate developers

Real estate developers in China are using mergers and acquisitions (M&As) to ensure their survival and competitiveness. However, no suitable method is yet available to assess whether such M&As provide enhanced value for those involved. Using a hybrid method of data envelopment analysis (DEA) and Malmquist total factor productivity (TFP) indices, this paper evaluates the short and medium term effects of M&As on acquirers’ economic performance with a set of 32 M&A cases occurring during 2000–2011 in China. The results of the analysis show that M&As generally have a positive effect on acquirers’ economic performance. Acquisitions on average experienced a steady growth in developer Malmquist TFP, a more progressive adoption of technology immediately after acquisition, a slight short-term decrease in technical efficiency after acquisition but followed by a marked increase in the longer term once the integration and synergy benefits were realised. However, there is no evidence to show whether developers achieved any short or long term scale efficiency improvements after M&A. The findings of this study provide useful insights on developer M&A performance from an efficiency and productivity perspective.

Cholesterol-Esterifying Enzymes in Developing Rat Brain

A cholesterol-esterifying enzyme which incorporates exogenous fatty acids into cholesterol esters in the presence of ATP and coenzyme A was demonstrated in 15-day-old rat brain. This enzyme was maximally active at pH 7.4 and distinct from the cholesterol-esterifying enzyme reported earlier (Eto and Suzuki, 1971), which has a pH optimum at 5.2 and does not require cofactors. Properties of the two enzymes have been compared. Both the enzymes showed negligible esterification with acetate and were maximally active with oleic acid. The pH 5.2 enzyme esterified desmosterol, lanosterol and cholesterol at about the same rate, while the pH 7.4 enzyme was only 50% as active ith lanosterol as it was with cholesterol and desmosterol. Phosphatidyl serine stimulated the pH 5.2 enzyme but not the pH 7.4 enzyme. Phosphatidyl choline and sodium taurocholate showed no effect on either of the enzymes. Both the enzymes were associated with particulate fractions, but the pH 7.4 enzyme was localized more in the microsomes. Purified myelin showed 2.6-fold and 1.5-fold higher specific activities of pH 5.2 and 7.4 enzymes respectively, when compared with homogenate. About 7-10% of total activity of both the enzymes was associated with purified myelin. Brain stem and spinal cord showed higher specific activity of pH 5.2 enzyme than cerebral cortex and cerebellum, while pH 7.4 enzyme specific activity was higher in cerebellum and brain stem than in cerebral cortex and spinal cord. Microsomal pH 7.4 activity showed progressive increase prior to the active period of myelination, reaching a maximum on the 15th day after birth and declined to 20% of the peak activity by 30 days. In contrast, pH 5.2 enzyme reached maximum activity about the 6th day after birth and remained at this level well into adulthood. In 15-day-old rat brain, pH 7.4 enzyme had five to six times higher specific activity than pH 5.2 enzyme, while in adults the activities were equal. The pH 7.4 enzyme showed a threefold higher specific activity than pH 5.2 enzyme in myelin from 15-day-old rats, but in adults the reverse was true. Key Words: Cholesterol esterifying enzymes-Developing rat brain-Myelination. Jagannatha H. M. and Sastry P. S. Cholesterol-esterifying enzymes in developing rat brain. J. Neurochem. 36, 1352- 1360 (1981).

Expression of cytochrome P450 enzymes and metabolism of timolol in human ocular tissue

Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.