Search results for: nonsense

Authors: Natalia V. Ursul

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In linguistic studies, the question of nonsense is attracting increasing interest. Nonsense is usually defined as spoken or written words that have no meaning. However, this definition is likely to be outdated as any speech act is generated due to the speaker’s pragmatic reasons, thus it cannot be purely illogical or meaningless. In the current paper a new working definition of nonsense as a linguistic medium will be formulated; moreover, the pragmatic peculiarities of newly coined linguistic patterns and possible ways of their interpretation will be discussed.

Keywords: nonsense, nonse verse, pragmatics, speech act

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Authors: Shahbaz Ahmed

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This study is conducted to demonstrate the knowledge of intentional learning and incidental learning. Hypothesis of this experiment is intentional learning is better than incidental learning, participants were demonstrated and were asked to learn the 10 nonsense syllables in a specific sequence from the colored cards in the end they were asked to recall the background color of each card instead of nonsense syllables. Independent variables of the experiment are the colored cards containing nonsense syllables which are to be memorized by the participants, dependent variables are the number of correct responses made by the participant. The findings of the experiment concluded that intentional learning is better than incidental learning, hence hypothesis is proved.

Keywords: intentional learning, incidental learning, non-sense syllable cards, score sheets

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Authors: Samia Al-Shayban

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Conventionally, Fielding Author’s Farce is read as an attack on literary and theatrical establishment. This paper attempt to read it as a disguised scathing political attack upon, King George II, his court and administration. Fielding achieves his design through complex dramatization based on implicit connections between King George II and the poor poet Luckless who shifts his stand from defending the liberties of the authors into becoming one of their oppressors. Through the same connection, the king is accused of being the originator and protector of literary corruption. To strengthen the attack against the king, the court of nonsense which appeared in Luckless’ play is connected to George II’s court through the presence of opera and ignorance. Thus, Fielding’s literary dramatization is used as a medium to expose the corrupting influence of the ruling elite. The King, his court and administration are all complacent in devaluing the English theatre and turning it into a circus that generate nothing but ignorance and poverty. This practice is deliberately designed to keep people ignorant and authors poor so they remain unable to challenge their corrupt politics.

Keywords: fielding, King George II, ignorance, theatre, plays

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Mafalda Moreira, Diana Alba, Inês Paiva Ferreira, Rita Calejo, Ana Rita Soares, Leonilde Machado

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Intellectual disability (ID) is characterized by deficits in intellectualfunctioningassociatedwithalterations in the adaptive behaviour, whose onset is inthedevelopmentalperiod. Itaffects 3% of the population, ofwhich 10% have a geneticaetiology. One of those causes isAlwadeiSyndrome, with 3 cases describedworldwide. It results from a homozygous nonsense mutation in theRUSC2 gene andisassociatedwithintellectualdisabilityanddysmorphic facialfeatures. Theauthorsreportthe case of a 5-year-old-boy, born to a healthymotherafter a full-termuneventfulpregnancy, thatwasreferred to Neurodevelopmentalconsultationdue toglobal developmentaldelay. Familyhistoryrevealedlearningdifficulties in the paternal brotherhood. Milddismorphicfeatureswereevidentsuch as darkinfraorbitalregion, low-set ears, beakednose, retrognathism, high-archedpalateandjointhyperlaxity. WechslerIntelligenceScale for Children III fullscaleIQ quoted 61. Karyotypeandchromosomalmicroarrayanalysiswerenormal, as well as the fragile X molecular study. DNA sequencingwasthenperformedandallowedtheidentificationof amutation in the RUSC2 gene. Theetiologicaldiagnosisof ID remains unknown in up to 80% of cases, creatinguncertainty in children’sfamilies. Theadvances in DNA sequencingtechnologieshaveincreasedourknowledgeofthegeneticdiseasesinvolved, as theAlwadeisyndromewasonlydescribedsince 2016. Thegeneticdiagnosisof ID allowsfamilygeneticcounselingandenablesthedevelopmentof target therapeutic approaches.

Keywords: intellectual disability, genetic aetiology, alwadei syndrome, RUSC2

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Authors: Patrizia Bonaventura

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The aim of this study is to analyze the influence of prosody on the acquisition of temporal aspects of V-V anticipatory lingual coarticulation in productions by Italian-speaking children. Two twin 7-years old male children, native Italian speakers, interacted with the same adult, repeating nonsense disyllables containing VtV sequences where V1 = {i, a} and V2 = {a,e, i, o,u}, with different stress patterns (e.g. pi’ta, pi’ta). The duration of the VC F2 transitions and the CV/VC F2 transitions durations ratios in different V2 contexts and stress conditions were measured by spectrographic analysis and compared between pronunciations by each child vs. the adult to test whether the child was able to imitate the duration of the transitions as produced by the adult in different stress conditions. Consequences highlighted a significant difference in durations of VC transitions between children and adult: longer VC transitions durations, indicating a greater amount of coarticulation, were found for one child in every context, and for the other, only in stressed [it] sequences. The data support the hypothesis of the presence of different temporal patterns of anticipatory coarticulation in adults and children, and of a greater amount of coarticulation in children, with different strategies of implementation across different prosodic conditions.

Keywords: speech acquisition, coarticulation, Italian language, prosody

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Authors: Imbesat Daudi

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One of the most discussed topics of the last century happens to be if Islamic civilization is violent. Many Western intellectuals have promoted the notion that Islamic civilization is violent. Citing 9/11, in which 3000 civilians were killed, they argue that Muslims are prone to violence because Islam promotes violence. However, Muslims reject this notion as nonsense. This topic has not been properly addressed. First, violence of civilizations cannot be proven by citing religious texts, which have been used in discussions over civilizational violence. Secondly, the question of whether Muslims are violent is inappropriate, as there is implicit bias suggesting that Islamic civilization is violent. A proper question should be which civilization is more violent. Third, whether Islamic civilization is indeed violent can only be established if more war-related casualties can be documented within the borders of Islamic civilization than that of their cohorts. This has never been done. Finally, the violent behavior of Muslim countries can be examined by comparing acts of violence committed by Muslim countries with acts of violence of groups of nations belonging to other civilizations by appropriate parameters of violence. Therefore, parameters reflecting group violence have been defined; violent conflicts of various civilizations of the last two centuries were documented, quantified by number of conflicts and number of victims, and compared with each other by following the established principles of statistics. The results show that whereas 80% of genocides and massacres were conducted by Western nations, less than 5% of acts of violence were committed by Muslim countries. Furthermore, the West has the highest incidence (new) and prevalence (new and old) of violent conflicts among all groups of nations. The result is unambiguous and statistically significant. Becoming informed can only be done by a methodical collection of relevant data, objective analysis of data, and unbiased information, a process which this paper follows.

Keywords: Islam and violence, demonization of Muslims, violence and the West, comparison of civilizational violence

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Authors: Montserrat Crespi Vallbona, Marta Domínguez Pérez

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Globalization impacts on cities and especially on their centers, especially on those spaces more visible and coveted. Changes are involved in processes such as touristification, gentrification or studentification, in addition of shop trendiness. The city becomes a good of interchange rather than a communal good for its inhabitants and consequently, its value is monetized. So, these different tendencies are analyzed: on one hand, the presence of tourists, the home rental increase, the explosion of businesses related to tourism; on the other hand; the return of middle classes or gentries to the center in a socio-spatial model that has changed highlighting the centers by their culture and their opportunities as well as by the value of public space and centrality; then, the interest of students (national and international) to be part of these city centers as dynamic groups and emerging classes with a higher purchasing power and better cultural capital than in the past; and finally, the conversion of old stores into modern ones, where vintage trend and the renewal of antiquity is the essence. All these transforming processes impact the European cities and redefine their image. All these trends reinforce the impression and brand of the urban center as an attractive space for investment, keeping such nonsense meaningful. These four tendencies have been spreading correlatively impacting the centers and transforming them involving the displacement of former residents of these spaces and revitalizing the center that is financed and commercialized in parallel. The cases of Madrid and Barcelona as spaces of greater evidence in Spain of these tendencies serve to illustrate these processes and represent the spearhead. Useful recommendations are presented to urban planners to find the conciliation of communal and commercialized spaces.

Keywords: gentrification, shop trendiness, studentification, touristification

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Authors: Nkatow Mafany Christian

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No other period in human history has offered such great opportunities for grievances not only to last long but also to be manifested across international boundaries. This state of affairs is likely a common feature of the advent of social media. The Anglophone Question in Cameroon has been a problem of poor constitutional arrangements that can be traced to 1961 when the former French Cameroon reunified with former British Southern Cameroons following a plebiscite in which the latter overwhelmingly voted to reunify with the former. Though Southern/Anglophone Cameroons complained of perceived marginalization and an attempt by the majority French section to assimilate them, the manifestation was subtle and took place only through protests, petitions, strikes movements and demonstrations. However, with the advent of social media, a new cream of leaders emerged in the diaspora, including the US, Canada, Europe, Asia and the Middle East, to champion the manifestations leading to violence and conflicts that have bedeviled the region since 2017. The feeling of political subjugation, economic exploitation, social suppression and cultural assimilation among Anglophone Cameroonians united them under diaspora leaders against the government of Cameroon, calling for the creation of a separate state for Anglophones. This paper draws from this lead-up to analyze the current Anglophone Crisis in Cameroon in the light of the Grievance Theory and Transnationalism. The paper makes an appeal to field experience, interviews, official sources, documentation, and the internet to succor its central thesis. From the fertility of its sources, the paper submits that social media is a potent source of conflicts and makes nonsense of the principle of sovereignty and territorial integrity by its capacity to promote the transnational manifestation of grievances.

Keywords: grievance, transnationalism, anglophone crisis, Cameroon, crisis and social media

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Ana Paula Soares, Alexandrina Lages, Helena Oliveira, Francisco-Javier Gutiérrez-Domínguez, Marisa Lousada

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From an early age, exposure to a spoken language allows us to implicitly capture the structure underlying the succession of the speech sounds in that language and to segment it into meaningful units (words). Statistical learning (SL), i.e., the ability to pick up patterns in the sensory environment even without intention or consciousness of doing it, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language and possibly to lie behind the language difficulties exhibited by children with development language disorder (DLD). The research conducted so far has, however, led to inconsistent results, which might stem from the behavioral tasks used to test SL. In a classic SL experiment, participants are first exposed to a continuous stream (e.g., syllables) in which, unbeknownst to the participants, stimuli are grouped into triplets that always appear together in the stream (e.g., ‘tokibu’, ‘tipolu’), with no pauses between each other (e.g., ‘tokibutipolugopilatokibu’) and without any information regarding the task or the stimuli. Following exposure, SL is assessed by asking participants to discriminate between triplets previously presented (‘tokibu’) from new sequences never presented together during exposure (‘kipopi’), i.e., to perform a two-alternative-forced-choice (2-AFC) task. Despite the widespread use of the 2-AFC to test SL, it has come under increasing criticism as it is an offline post-learning task that only assesses the result of the learning that had occurred during the previous exposure phase and that might be affected by other factors beyond the computation of regularities embedded in the input, typically the likelihood two syllables occurring together, a statistic known as transitional probability (TP). One solution to overcome these limitations is to assess SL as exposure to the stream unfolds using online techniques such as event-related potentials (ERP) that is highly sensitive to the time-course of the learning in the brain. Here we collected ERPs to examine the neurofunctional correlates of SL in preschool children with DLD, and chronological-age typical language development (TLD) controls who were exposed to an auditory stream in which eight three-syllable nonsense words, four of which presenting high-TPs and the other four low-TPs, to further analyze whether the ability of DLD and TLD children to extract-word-like units from the steam was modulated by words’ predictability. Moreover, to ascertain if the previous knowledge of the to-be-learned-regularities affected the neural responses to high- and low-TP words, children performed the auditory SL task, firstly, under implicit, and, subsequently, under explicit conditions. Although behavioral evidence of SL was not obtained in either group, the neural responses elicited during the exposure phases of the SL tasks differentiated children with DLD from children with TLD. Specifically, the results indicated that only children from the TDL group showed neural evidence of SL, particularly in the SL task performed under explicit conditions, firstly, for the low-TP, and, subsequently, for the high-TP ‘words’. Taken together, these findings support the view that children with DLD showed deficits in the extraction of the regularities embedded in the auditory input which might underlie the language difficulties.

Keywords: development language disorder, statistical learning, transitional probabilities, word segmentation

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