Waste management practices in tourism destinations of Finnish Lapland

Tourism in Finland holds a significant position in Finnish economy, extending from Southern to Northern Finland, and sustainable tourism is being heavily promoted nowadays. This study focuses on waste management practices as one of many important topics related to sustainability and sustainable tourism, implementing qualitative data analysis, and applying practice theory as a theoretical approach. The research subject revolves around understanding the current situation of solid waste management in tourism, how existing issues in certain practices are addressed, and how the whole waste management system can be improved. Four semi-structured thematic interviews were conducted with stakeholders in the tourism industry, namely Destination Marketing Organization (DMO), academic, waste management company, and tourism resort. The findings conclude that the practices generating the most waste in Lapland are related to consumption, biowaste, and building projects, which further supports literature that discusses these practices. Recommendations for improvement mostly revolve around implementing local waste treatment possibilities, in addition to increased education, raising awareness, and close collaboration, utilizing a multichannel approach in these. The study also recommends further research on the status of waste beyond collection, in addition to exploring the possibilities of adopting innovative waste management practices that have been successfully implemented in different parts of Europe. The study was limited in the sense that it did not involve a case study due to the anonymity of the participants, which present an opportunity in the future for area-specific studies for waste management practices in Lapland

The Role of Beta Subunit Variant on the Properties of Delta-Containing Extrasynaptic GABAA Receptors

Muscimol, a psychoactive constituent of Amanita muscaria, activates all GABAA receptor subtypes with exceptionally high affinity to αβδ. This is explained by δ subunit role on muscimol extremely slow dissociation from these receptors. However, the contributions of GABAAR β subunit variant to the affinity state of αβδ receptors and function were not described in similar detail as α subunit variant in the literature. The extrasynaptic δ-containing receptors are in a great deal responsible for the so-called tonic inhibition in the brain. This study aims to understand the role of β1,2,3 subunits in muscimol binding to δ-containing extrasynaptic GABAA receptors. We performed transient expression of recombinant GABAAR subtypes in HEK293 cells and determined the association and dissociation rates of [3H]muscimol binding to recombinant α6β1δ, α6β2δ and α6β3δ receptors using radiolabeled binding kinetics approaches. α6β1,2,3δ recombinant receptors showed distinct binding kinetics. In α6β1δ and α6β2δ recombinant receptors, [3H]muscimol association was similar and significantly slower than α6β3δ. Moreover, dissociation of the binding was very slow especially to α6β2δ recombinant receptor compared to α6β1δ and α6β3δ that were similar. The remarkable slow dissociation of [3H]muscimol from all three receptor subtypes confirms the studies indicating α6β1-3δ high affinity state being independent of β subunit. Further electrophysiological studies are needed to reveal how different β subunits affect binding site of αβδ GABAA receptors in terms of ligand sensitivity and efficacy. This leads to an improved pharmacological characterization of extrasynaptic αβδ receptors and possible development of selective allosteric modulators with therapeutic significance for alcoholism, anesthesia and epilepsy.Siirretty Doriast

Nature’s brewery to bedtime: The Role of hops in GABAA receptor modulation and sleep promotion

Insomnia, a prevalent health challenge, often requires pharmacological interventions to improve sleep onset, maintenance, and quality. Benzodiazepines and Z-drugs, like other positive modulators, enhance the inhibitory effects of gamma-aminobutyric acid (GABA) by stabilizing the open conformation of the GABAA receptor (GABAAR) chloride ion channels, facilitating the transition to sleep. However, prolonged use raises concerns, including dependence and cognitive issues. Among herbal alternatives, Humulus lupulus (hops) is gaining attention due to its role as a natural relaxant, sleep aid, and brewing component. Neuroactive phytochemicals in hops may modulate GABAARs differently from benzodiazepines. This research uncovers these hop constituents and potential therapeutic mechanisms. The α-acid humulone and hop prenylflavonoids (PFs), including xanthohumol/isoxanthohumol, 6/8-prenylnaringenin, enhanced GABA-induced displacement of [3H]EBOB, a GABAAR function marker, in the low micromolar range. These potent effects were flumazenil-insensitive and α6β3δ subtype-selective. Molecular docking at the α1β2γ2 isoform identified the extracellular α+/β− interface as the PF binding site. An additional 6-prenylnaringenin site was recognized at the extracellular α+/γ2− interface, aligning with its inhibition of [3H]flunitrazepam and [3H]Ro 15-4513 binding. Given humulone’s prominence and relatively high potency, its activity was confirmed electrophysiologically, where it enhanced GABA-evoked currents in the sedation-mediating α1β3γ2 subtype. In mice, humulone reduced locomotor activity, shortened sleep onset induced by pentobarbital, and prolonged sleep duration induced by either pentobarbital or ethanol. Moreover, [3H]EBOB binding assays showed synergies between humulone and ethanol, and additive interactions with PFs, suggesting enhanced alcohol intoxication in hop-rich beers. In summary, we revealed positive modulators of GABAARs that act independently of the classical benzodiazepine site. 6-prenylnaringenin also acts as a silent modulator with the potential to block benzodiazepine responses. Humulone plays a pivotal role in the sedative and sleep-promoting properties of hops. These findings offer novel mechanistic insights into hop neuroactive constituents and potential avenues for sleep aid optimization.Luonnon panimosta apua nukahtamiseen: Humalan vaikutuksesta GABAA-reseptoriin ja unen edistämiseen Pitkäaikainen unettomuus on terveysriski, joka voi vaatia lääkehoitoa parantamaan unen alkamista, ylläpitoa ja laatua. Bentsodiatsepiinit ja muut positiiviset säätelijät, vahvistavat gamma-aminovoihapon (GABA) estäviä vaikutuksia vakauttamalla GABAA-reseptorin (GABAAR) kloridikanavan avointa muotoa ja helpottavat nukahtamista. Kuitenkin pitkäaikaisen käytön seurauksena voi syntyä haittoja, kuten riippuvuutta ja kognitiivisia ongelmia. Humalalla (Humulus lupulus) on pitkät perinteet luonnollisena rauhoittavana ja unilääkkeenä sekä merkittävä rooli panimoteollisuudessa. Humalan neuroaktiiviset fytokemikaalit saattavat säädellä GABAAR:a eri tavalla kuin bentsodiatsepiinit. Tämä tutkimus pyrki selvittämään näitä humalan yhdisteitä ja niiden mahdollisia terapeuttisia mekanismeja. Humalan prenyyliflavonoidit ksantohumoli, isoksantohumoli, 6- ja 8-prenyylinaringeniini sekä α-happo humuloni tehostivat GABAAR-toimintaa. Nämä alhaisten mikro-molaaristen pitoisuuksien vaikutukset olivat selektiivisempiä α6β3δ- alatyypille ja epä-herkkiä flumatseniilille. Sitoutumisennuste molekulaarisen telakoinnin avulla α1β2γ2 reseptorialatyypissä paljasti solunulkoisen α+/β—alayksikkörajapinnan prenyyliflavonoidien vahvistamisen sitoutumiskohtana. Lisäpaikka 6-prenyylinaringeniinille tunnistettiin solunulkoisessa α+/γ2−-rajapinnassa, mikä sopii sen aiheuttamaan [3H]flunitratse-paamin ja [3H]Ro 15-4513:n sitoutumisen estoon samassa kohdassa. Ottaen huomioon humulonin suuren pitoisuuden humalassa tutkimme sen vaikutusta GABAAR:in toimintaan sähköfysiologisesti. Humuloni tehosti GABAn aikaansaamia virtoja sedaatiota välittävässä α1β3γ2-alatyypissä. Se inhiboi hiirten spontaania liikeaktiivisuutta ja lisäsi pentobarbitaalin ja etanolin aiheuttaman unen kestoa. [3H]EBOB-sitoutumiskokeet paljastivat yhteisvaikutuksia humulonin, prenyyliflavonoidien ja etanolin välillä, mikä viittaa alkoholin vaikutusten tehostamiseen humalapitoisissa oluissa. Löysimme humalasta GABAAR:ien positiivisia säätelijöitä, jotka vaikuttivat ilman klassista bentsodiatsepiinien sitoutumispaikkaa. 6-prenyylinaringeniini toimi myös hiljaisena säätelijänä, jolla on potentiaalia estää bentsodiatsepiinivasteita. Humulonilla on keskeinen rooli humalan sedatiivisissa ja unta edistävissä ominaisuuksissa. Nämä löydökset tarjoavat uusia mekanistisia näkemyksiä humalan neuroaktiivisista yhdisteistä sekä aihioita olemassa olevien unilääkkeiden paranteluun

Model tracking for risk problems

We assume that we have M candidate insurance models for describing a process. The models considered consist of a risk process driven by right-constant, finite-state spaces, jump processes. Based on observing the history of the risk process, we propose dynamics whose solutions indicate the likelihoods of each candidate model

Bounds for graphs of given girth and generalized polygons

In this paper we present a bound for bipartite graphs with average bidegrees η and ξ satisfying the inequality η ≥ ξ α, α ≥ 1. This bound turns out to be the sharpest existing bound. Sizes of known families of finite generalized polygons are exactly on that bound. Finally, we present lower bounds for the numbers of points and lines of biregular graphs (tactical configurations) in terms of their bidegrees. We prove that finite generalized polygons have smallest possible order among tactical configuration of given bidegrees and girth. We also present an upper bound on the size of graphs of girth g ≥ 2t + 1. This bound has the same magnitude as that of Erd¨os bound, which estimates the size of graphs without cycles C₂t

Partially Observed Discrete-valued Time Series

The analysis of time series of counts is a rapidly developing area. It has very broad application in view of the host of integer-valued time series which cannot be satisfactorily handled within the classical framework of Gaussian- like series. In this paper we derive recursive filters for partially observed discrete-valued time series. These processes are regulated by thinning binomial and multinomial operators (to be defined below).Анализ временных последовательностей отсчетов — интенсивно развивающееся направление. Такой анализ широко используется для базовых целочисленных временных последовательностей, с которыми нельзя удовлетворительно работать в рамках классических последовательностей гауссовa типа. Получены рекурсивные фильтры для частично наблю даемых дискретизированных временных последовательностей. Показано, что эти процессы регулируются прореживающими биномиальными и полиномиальными операторами.Аналіз часових послідовностей відліків — напрям, що інтенсивно розвивається. Такий аналіз широко використовується для базових цілочисельних часових послідовностей, з якими не можна задовільно працювати у рамках класичних послідовностей гаусовa типу. Отримано рекурсивні фільтри для частково спостерігаємих дискретизованих часових послідовностей. Показано, що ці процеси регулюються проріжуючими біноміальними та поліноміальними операторами

The Influence of AA29504 on GABA A Receptor Ligand Binding Properties and Its Implications on Subtype Selectivity

The unique pharmacological properties of δ-containing γ-aminobutyric acid type A receptors (δ-GABAARs) make them an attractive target for selective and persistent modulation of neuronal excitability. However, the availability of selective modulators targeting δ-GABAARs remains limited. AA29504 ([2-amino-4-(2,4,6-trimethylbenzylamino)-phenyl]-carbamic acid ethyl ester), an analog of K+ channel opener retigabine, acts as an agonist and a positive allosteric modulator (Ago-PAM) of δ-GABAARs. Based on electrophysiological studies using recombinant receptors, AA29504 was found to be a more potent and effective agonist in δ-GABAARs than in γ2-GABAARs. In comparison, AA29504 positively modulated the activity of recombinant δ-GABAARs more effectively than γ2-GABAARs, with no significant differences in potency. The impact of AA29504's efficacy- and potency-associated GABAAR subtype selectivity on radioligand binding properties remain unexplored. Using [3H]4'-ethynyl-4-n-propylbicycloorthobenzoate ([3H]EBOB) binding assay, we found no difference in the modulatory potency of AA29504 on GABA- and THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol)-induced responses between native forebrain GABAARs of wild type and δ knock-out mice. In recombinant receptors expressed in HEK293 cells, AA29504 showed higher efficacy on δ- than γ2-GABAARs in the GABA-independent displacement of [3H]EBOB binding. Interestingly, AA29504 showed a concentration-dependent stimulation of [3H]muscimol binding to γ2-GABAARs, which was absent in δ-GABAARs. This was explained by AA29504 shifting the low-affinity γ2-GABAAR towards a higher affinity desensitized state, thereby rising new sites capable of binding GABAAR agonists with low nanomolar affinity. Hence, the potential of AA29504 to act as a desensitization-modifying allosteric modulator of γ2-GABAARs deserves further investigation for its promising influence on shaping efficacy, duration and plasticity of GABAAR synaptic responses