LegalLens: Leveraging LLMs for Legal Violation Identification in Unstructured Text

In this study, we focus on two main tasks, the first for detecting legal violations within unstructured textual data, and the second for associating these violations with potentially affected individuals. We constructed two datasets using Large Language Models (LLMs) which were subsequently validated by domain expert annotators. Both tasks were designed specifically for the context of class-action cases. The experimental design incorporated fine-tuning models from the BERT family and open-source LLMs, and conducting few-shot experiments using closed-source LLMs. Our results, with an F1-score of 62.69\% (violation identification) and 81.02\% (associating victims), show that our datasets and setups can be used for both tasks. Finally, we publicly release the datasets and the code used for the experiments in order to advance further research in the area of legal natural language processing (NLP)

Glutamate-mediated blood-brain barrier opening. implications for neuroprotection and drug delivery

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders

A synthetic biology approach for evaluating the functional contribution of designer cellulosome components to deconstruction of cellulosic substrates

BACKGROUND: Select cellulolytic bacteria produce multi-enzymatic cellulosome complexes that bind to the plant cell wall and catalyze its efficient degradation. The multi-modular interconnecting cellulosomal subunits comprise dockerin-containing enzymes that bind cohesively to cohesin-containing scaffoldins. The organization of the modules into functional polypeptides is achieved by intermodular linkers of different lengths and composition, which provide flexibility to the complex and determine its overall architecture. RESULTS: Using a synthetic biology approach, we systematically investigated the spatial organization of the scaffoldin subunit and its effect on cellulose hydrolysis by designing a combinatorial library of recombinant trivalent designer scaffoldins, which contain a carbohydrate-binding module (CBM) and 3 divergent cohesin modules. The positions of the individual modules were shuffled into 24 different arrangements of chimaeric scaffoldins. This basic set was further extended into three sub-sets for each arrangement with intermodular linkers ranging from zero (no linkers), 5 (short linkers) and native linkers of 27–35 amino acids (long linkers). Of the 72 possible scaffoldins, 56 were successfully cloned and 45 of them expressed, representing 14 full sets of chimaeric scaffoldins. The resultant 42-component scaffoldin library was used to assemble designer cellulosomes, comprising three model C. thermocellum cellulases. Activities were examined using Avicel as a pure microcrystalline cellulose substrate and pretreated cellulose-enriched wheat straw as a model substrate derived from a native source. All scaffoldin combinations yielded active trivalent designer cellulosome assemblies on both substrates that exceeded the levels of the free enzyme systems. A preferred modular arrangement for the trivalent designer scaffoldin was not observed for the three enzymes used in this study, indicating that they could be integrated at any position in the designer cellulosome without significant effect on cellulose-degrading activity. Designer cellulosomes assembled with the long-linker scaffoldins achieved higher levels of activity, compared to those assembled with short-and no-linker scaffoldins. CONCLUSIONS: The results demonstrate the robustness of the cellulosome system. Long intermodular scaffoldin linkers are preferable, thus leading to enhanced degradation of cellulosic substrates, presumably due to the increased flexibility and spatial positioning of the attached enzymes in the complex. These findings provide a general basis for improved designer cellulosome systems as a platform for bioethanol production

Assembly of Xylanases into Designer Cellulosomes Promotes Efficient Hydrolysis of the Xylan Component of a Natural Recalcitrant Cellulosic Substrate

In nature, the complex composition and structure of the plant cell wall pose a barrier to enzymatic degradation. Nevertheless, some anaerobic bacteria have evolved for this purpose an intriguing, highly efficient multienzyme complex, the cellulosome, which contains numerous cellulases and hemicellulases. The rod-like cellulose component of the plant cell wall is embedded in a colloidal blend of hemicelluloses, a major component of which is xylan. In order to enhance enzymatic degradation of the xylan component of a natural complex substrate (wheat straw) and to study the synergistic action among different xylanases, we have employed a variation of the designer cellulosome approach by fabricating a tetravalent complex that includes the three endoxylanases of Thermobifida fusca (Xyn10A, Xyn10B, and Xyn11A) and an Xyl43A β-xylosidase from the same bacterium. Here, we describe the conversion of Xyn10A and Xyl43A to the cellulosomal mode. The incorporation of the Xyl43A enzyme together with the three endoxylanases into a common designer cellulosome served to enhance the level of reducing sugars produced during wheat straw degradation. The enhanced synergistic action of the four xylanases reflected their immediate juxtaposition in the complex, and these tetravalent xylanolytic designer cellulosomes succeeded in degrading significant (~25%) levels of the total xylan component of the wheat straw substrate. The results suggest that the incorporation of xylanases into cellulosome complexes is advantageous for efficient decomposition of recalcitrant cellulosic substrates—a distinction previously reserved for cellulose-degrading enzymes

Central nervous system lymphatic unit, immunity, and epilepsy : Is there a link?

Summary The recent definition of a network of lymphatic vessels in the meninges surrounding the brain and the spinal cord has advanced our knowledge on the functional anatomy of fluid movement within the central nervous system (CNS). Meningeal lymphatic vessels along dural sinuses and main nerves contribute to cerebrospinal fluid (CSF) drainage, integrating the cerebrovascular and periventricular routes, and forming a circuit that we here define as the CNS-lymphatic unit. The latter unit is important for parenchymal waste clearance, brain homeostasis, and the regulation of immune or inflammatory processes within the brain. Disruption of fluid drain mechanisms may promote or sustain CNS disease, conceivably applicable to epilepsy where extracellular accumulation of macromolecules and metabolic by-products occur in the interstitial and perivascular spaces. Herein we address an emerging concept and propose a theoretical framework on: (a) how a defect of brain clearance of macromolecules could favor neuronal hyperexcitability and seizures, and (b) whether meningeal lymphatic vessel dysfunction contributes to the neuroimmune cross-talk in epileptic pathophysiology. We propose possible molecular interventions targeting meningeal lymphatic dysfunctions, a potential target for immune-mediated epilepsy.Peer reviewe

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Psyykkisen valmennuksen konseptin kehittäminen Lapin urheiluakatemian yläkoululeiritykseen

Opinnäytetyömme käsittelee psyykkisen valmennuksen konseptin kehittämistä Lapin urheiluakatemialle. Kohderyhmänä ovat eri lajien 13 – 16-vuotiaat kahdeksas- ja yhdeksäsluokkalaiset yläkouluakatemiaurheilijat. Opinnäytetyömme on toiminnallinen tapaustutkimus. Työmme sisältää raporttiosan ja tuotoksen. Tiedonkeruun toteutimme tutkimalla aiheeseen liittyvää suomen- ja englanninkielistä kirjallisuutta sekä haastattelemalla työntilaajan edustajia. Laatimamme psyykkisen valmennuksen konsepti on testattu jo käytännössä ensimmäisellä Lapin urheiluakatemian yläkouluakatemialeirillä heinäkuussa 2014. Lopputuotoksena syntynyt psyykkisen valmennuksen konsepti tarjoaa leirimuotoisessa yläkouluakatemiavalmennuksessa mukana oleville urheilijoille johdonmukaisesti etenevää psyykkistä valmennusta kahden vuoden ajan. Kerätyn teoriatiedon pohjalta hyödynnämme urheilijoiden opetuksessa paljon yhteistoiminnallista oppimista ja pienryhmätyöskentelyä. Yläkouluakatemian urheilijat edustavat niin sanottuja Y- ja Z- sukupolvea, jotka arvostavat erityisesti aktiivista vuorovaikutusta valmennustilanteissa. Opetustyyleistä parhaiten haasteeseen vastaa yhteistoiminnallinen oppiminen, jota konseptissa hyödynnämme aktiivisesti. Työssämme korostuu kehityspsykologian merkitys tutkittaessa nuorten valmiuksia omaksua psyykkistä valmennusta nuorella iällä. Yhdistämällä psyykkisen valmennuksen ja kehityspsykologian teorioita olemme päässeet tulokseen, jonka mukaan nuorilla on kaikki valmiudet omaksua psyykkisen valmennuksen perustaitoja jo 13–16-vuotiaina. Psyykkisellä valmennuksella voi olla myös positiivinen vaikutus nuorten urheilijoiden burnout- ja drop-out-ilmiöiden ennaltaehkäisyssä. Tärkeänä asiana esiin nousi myös tehtäväsuuntautuneen motivaatioilmaston edut verrattuna kilpailusuuntautuneeseen motivaatioilmastoon valmennustilanteissa.This thesis deals with the development of the concept of mental coaching for the Lapland Sport Academy. The target group was the secondary school eighth and ninth grader sports academy athletes. The individuals in the group were between the ages of 13 and 16 from various different sports. This is a functional case study. The work includes a report, and a product. The data collection was conducted by researching Finnish and English literature of the topic, and by interviewing the representatives of the commissioner. The planned mental training concept has already been tested in practice during the first secondary school Lapland sports academy camp in July 2014. The resulting mental coaching concept offers progressive coaching for athletes in the camp style secondary school academy coaching. The secondary school academy athletes represent the so-called Y and Z generations who appreciate especially active interaction in coaching. We compared different teaching styles and found out that cooperative learning was the best suited for our purpose and for the young athletes. According to the collected theoretical data we utilize a lot of cooperative learning, and working in small groups in athlete coaching. The importance of developmental psychology is emphasized in our work when examining the ability to adapt mental coaching at a young age. By combining mental coaching and developmental psychological theories we have come to the conclusion that all young people have the capacity to embrace the psychological training of basic skills already at the age of 13 to 16. Mental coaching can have a positive effect on young athlete´s burnout and drop-out prevention. A significant point was also the process oriented motivational climate advantages compared to the goal oriented climate in coaching.Työ sisältää teorian pohjalta luodun psyykkisen valmennuksen konseptin. Konseptissa on luentoja, käytännön harjoitteita ja kotitehtäviä

Motivaatio- ja Itsensä johtaminen -moduulien rakentaminen "Skills4Life -Taidot elämään" hankkeelle

Tämä opinnäytetyö, Motivaatio- ja Itsensä johtaminen -moduulien rakentaminen ”Skills4Life – Taidot elämään” liittyy laajempaan kokonaisuuteen Lapin Urheiluopiston ja Lapin ammattikorkeakoulun välisessä yhteistyössä. Tämän yhteistyön laajempana tarkoituksena on rakentaa 30 opintopisteen kokonaisuus taidon oppimisesta, koska puutteelliset liikuntataidot ovat yksi syy siihen, miksi ihmiset liikkuvat nykyään liian vähän. Puutteelliset liikuntataidot muodostavat paitsi henkisen esteen harrastuksen aloittamiselle, mutta myös lisäävät loukkaantumisriskiä. Hankkeen avulla nykytutkimukseen perustuvaa tietoa taidon oppimisesta voidaan hyöyntää paremmin liikunnassa ja urheilussa. Käsillä olevan kehittämistyön tavoitteena oli rakentaa tähän hankkeeseen 5 opintopisteen moduulit motivaatiosta sekä itsensä johtamisesta, jotka olisivat toteutettavissa etäopintoina openmoodle alustalla. Toimeksiannon mukaan moduulien oli tarkoitus sisältää teoriatietoa ja tehtäviä motivaatiosta sekä itsensä johtamisesta. Moduulien ensisijaisena kohderyhmänä ovat valmentajat, ohjaajat, urheilijat sekä liikunta-alan opiskelijat. Kehittämistyö toteutettiin yhdessä Lapin Urheiluopiston sekä Lapin AMK:n asiantuntijoiden kanssa. Kehittämistyössä keskeisessä osassa on teoria motivaatiosta ja itsensä johtamisesta. Tätä teoriaosuutta käytettiin apuna sisältöjen rakentamisessa Skills4Life -verkkoympäristöön. Opintokokonaisuudet saatiin valmiiksi kesällä 2020, jonka jälkeen motivaatio sekä itsensä johtamisen -moduuleita on koekäytetty ja sen pohjalta kerätty palautetta. Työn tuotoksena syntyi viiden opintopisteen kokonaisuudet motivaatiosta sekä itsensä johtamisesta. Nämä opintokokonaisuudet ovat mahdollista toteuttaa täysin etänä openmoodlessa, mikä mahdollistaa opintojen suorittamisen ympäri Suomea tai ulkomailta. Työn tuotoksena tuli myös materiaalia, josta pystyy tulevaisuudessa rakentamaan koulutuksia, joissa hyödynnetään niin lähi- kuin etäopetusta

Interplay between Clostridium thermocellum Family 48 and Family 9 Cellulases in Cellulosomal versus Noncellulosomal States▿ †

The anaerobic, thermophilic cellulolytic bacterium Clostridium thermocellum is known for its elaborate cellulosome complex, but it also produces a separate free cellulase system. Among the free enzymes, the noncellulosomal enzyme Cel9I is a processive endoglucanase whose sequence and architecture are very similar to those of the cellulosomal enzyme Cel9R; likewise, the noncellulosomal exoglucanase Cel48Y is analogous to the principal cellulosomal enzyme Cel48S. In this study we used the designer cellulosome approach to examine the interplay of prominent cellulosomal and noncellulosomal cellulases from C. thermocellum. Toward this end, we converted the cellulosomal enzymes to noncellulosomal chimeras by swapping the dockerin module of the cellulosomal enzymes with a carbohydrate-binding module from the free enzyme analogues and vice versa. This enabled us to study the importance of the targeting effect of the free enzymes due to their carbohydrate-binding module and the proximity effect for cellulases on the designer cellulosome. C. thermocellum is the only cellulosome-producing bacterium known to express two different glycoside hydrolase family 48 enzymes and thus the only bacterial system that can currently be used for such studies. The different activities with crystalline cellulose were examined, and the results demonstrated that the individual chimeric cellulases were essentially equivalent to the corresponding wild-type analogues. The wild-type cellulases displayed a synergism of about 1.5-fold; the cellulosomal pair acted synergistically when they were converted into free enzymes, whereas the free enzymes acted synergistically mainly in the wild-type state. The targeting effect was found to be the major factor responsible for the elevated activity observed for these specific enzyme combinations, whereas the proximity effect appeared to play a negligible role