Irregularity of the <ie> Spellings in West-Saxon: The Problem of Pronouns

Orthographic consistency was rarely maintained in most Old English varieties, because the language system was relatively new and spelling norms took time to develop. While full standardisation is never expected in Old English, the understanding of factors underlying patterns of regularity and irregularity are paramount for a full grasp of issues pertaining to authorship, textuality and other linguistic and non-linguistic levels of analysis. These notes explore spelling irregularity in material from West Saxon dialects, bringing comparative examples of variation in spelling between early West Saxon (eWS) and late West Saxon (lWS) . West Saxon generally stands up for its emphasis on some degree of orthographic standardisation and yet appears to display interesting patterns of variation. The focus of my notes will be on particular instances of spelling inconsistencies, with special attention to a specific category of words where appears to vary more frequently, namely third-person pronouns. For my exploratory analysis, various witnesses of the Anglo-Saxon Chronicle (i.e. examples of eWS and lWS texts) were compared. The data was collected from different sections of an orthography-friendly edition of four different manuscripts, MSA (Bately 1986), MSB (Taylor 1983), MSC (O’Brien O’Keefe 2001) and MSD (Cubbin 1996), and compared with digital copies of the original manuscripts. The latter part of these notes points to some of the factors which could explain the features detected, with an exhortation for future researchers to build on some of the ideas proposed and explore new territory

Special Edition: 3rd International Postgraduate Conference on Modern Foreign Languages, Linguistics and Literature

The 3rd International Conference on Modern Foreign Languages, Linguistics and Literature took place in Preston, United Kingdom, on June 20, 2016. The conference was organised with the support of the School of Language, Literature and International Studies (now School of Humanities and Social Sciences) of the University of Central Lancashire, under the umbrella of the Research Excellence Framework, the new system for assessing the quality of research in UK higher education institutions (co-ordinated by Dr Michael Thomas). The conference was aimed at giving early-career researchers the opportunity to disseminate their research and to network with other researchers, and it was attended by more than 80 people, among which 33 speakers from different corners of the British Isles, and from abroad, including countries such as Bulgaria, Ireland, Italy, Spain, the Netherlands, Tunisia, Saudi Arabia, USA, Thailand, China and India. The success of the conference is also owed to the excellent supporting team of volunteers who helped out on the day, and especially Dr Oris Tom-Lawyer, Miguel Angel Saona-Vallejos, Mawaheb Khojah and Baetty from the University of Central Lancashire. The conference was also attended by our guest keynote speaker Prof. Hayo Reinders, currently Dean of the Graduate School of Education and Director of the Anaheim University Doctor of Education (Ed.D.) in TESOL Program

Preface to the special edition

The 4th International Conference on Modern Foreign Languages, Linguistics and Literature was held at the University of Central Lancashire in the UK on 1st June 2017. The six papers collected in this special edition of the Journal of Second Language Teaching and Research have been developed from papers first delivered at the event which brought together over thirty presentations in total from presenters in ten countries. Largely focused on giving opportunities to postgraduate research students to acquire valuable experience of conference participation and attendance, the event also included early career researchers, and addressed a wide range of research topics across theoretical and applied linguistics, as well as literary and cultural studies

Special Edition: 4th International Postgraduate Conference on Modern Foreign Languages, Linguistics and Literature

The 4th International Conference on Modern Foreign Languages, Linguistics and Literature was held at the University of Central Lancashire in the UK on 1st June 2017. The six papers collected in this special edition of the Journal of Second Language Teaching and Research have been developed from papers first delivered at the event which brought together over thirty presentations in total from presenters in ten countries. Largely focused on giving opportunities to postgraduate research students to acquire valuable experience of conference participation and attendance, the event also included early career researchers, and addressed a wide range of research topics across theoretical and applied linguistics, as well as literary and cultural studies

Celecoxib inhibits proliferation and survival of chronic myelogeous leukemia (CML) cells via AMPK-dependent regulation of β-catenin and mTORC1/2.

CML is effectively treated with tyrosine kinase inhibitors (TKIs). However, the efficacy of these drugs is confined to the chronic phase of the disease and development of resistance to TKIs remains a pressing issue. The anti-inflammatory COX2 inhibitor celecoxib has been utilized as anti-tumour drug due to its anti-proliferative activity. However, its effects in hematological malignancies, in particular CML, have not been investigated yet. Thus, we tested biological effects and mechanisms of action of celecoxib in Philadelphia-positive (Ph+) CML and ALL cells.We show here that celecoxib suppresses the growth of Ph+ cell lines by increasing G1-phase and apoptotic cells and reducing S- and G2-phase cells. These effects were independent of COX2 inhibition but required the rapid activation of AMP-activated protein kinase (AMPK) and the consequent inhibition mTORC1 and 2. Treatment with celecoxib also restored GSK3β function and led to down-regulation of β-catenin activity through transcriptional and post-translational mechanisms, two effects likely to contribute to Ph+ cell growth suppression by celecoxib.Celecoxib inhibited colony formation of TKI-resistant Ph+ cell lines including those with the T315I BCR-ABL mutation and acted synergistically with imatinib in suppressing colony formation of TKI-sensitive Ph+ cell lines. Finally, it suppressed colony formation of CD34+ cells from CML patients, while sparing most CD34+ progenitors from healthy donors, and induced apoptosis of primary Ph+ ALL cells.Together, these findings indicate that celecoxib may serve as a COX2-independent lead compound to simultaneously target the mTOR and β-catenin pathways, key players in the resistance of CML stem cells to TKIs

Carbon Isotope Composition and the NDVI as Phenotyping Approaches for Drought Adaptation in Durum Wheat: Beyond Trait Selection

High-throughput phenotyping platforms provide valuable opportunities to investigate biomass and drought-adaptive traits. We explored the capacity of traits associated with drought adaptation such as aerial measurements of the Normalized Difference Vegetation Index (NDVI) and carbon isotope composition (δ13C) determined at the leaf level to predict genetic variation in biomass. A panel of 248 elite durum wheat accessions was grown at the Maricopa Phenotyping platform (US) under well-watered conditions until anthesis, and then irrigation was stopped and plot biomass was harvested about three weeks later. Globally, the δ13C values increased from the first to the second sampling date, in keeping with the imposition of progressive water stress. Additionally, δ13C was negatively correlated with final biomass, and the correlation increased at the second sampling, suggesting that accessions with lower water-use efficiency maintained better water status and, thus, performed better. Flowering time affected NDVI predictions of biomass, revealing the importance of developmental stage when measuring the NDVI and the effect that phenology has on its accuracy when monitoring genotypic adaptation to specific environments. The results indicate that in addition to choosing the optimal phenotypic traits, the time at which they are assessed, and avoiding a wide genotypic range in phenology is crucial

Unusual Signs and Symptoms in HIV-Positive Patients Coinfected with Leishmania spp: The Importance of Neglected Tropical Disease in Differential Diagnosis

Leishmaniasis is a parasitic disease affecting both animals and humans, acquired with the bite of sand flies or, in Injection Drug Users (IDUs), with contaminated needles, still hypoendemic in Sicily and the Mediterranean basin. Even though it is responsible for 20,000 to 40,000 deaths per year, this parasitic infection is still considered a neglected tropical disease. People Living with HIV (PLWH) are considered at high-risk of developing Leishmaniasis and, despite the introduction of Highly Active Anti-Retroviral Therapy (HAART), mortality rate and relapses prevalence are still high in coinfected people.We present a case of HIV-Leishmania coinfection, posing the attention on the atypical signs and symptoms and the importance of thinking about other causes than the HIV infection progression when the patient presents with a worsening of his immune status during HAART

Proteasome-mediated degradation of keratins 7, 8, 17 and 18 by mutant KLHL24 in a foetal keratinocyte model: Novel insight in congenital skin defects and fragility of epidermolysis bullosa simplex with cardiomyopathy

Epidermolysis bullosa simplex (EBS) with cardiomyopathy (EBS-KLHL24) is an EBS subtype caused by dominantly inherited, gain-of-function mutations in the gene encoding for the ubiquitin-ligase KLHL24, which addresses specific proteins to proteasomal degradation. EBS-KLHL24 patients are born with extensive denuded skin areas and skin fragility. Whilst skin fragility rapidly ameliorates, atrophy and scarring develop over time, accompanied by life-threatening cardiomyopathy. To date, pathogenetic mechanisms underlying such a unique disease phenotype are not fully characterized. The basal keratin 14 (K14) has been indicated as a KLHL24 substrate in keratinocytes. However, EBS-KLHL24 pathobiology cannot be determined by the mutation-enhanced disruption of K14 alone, as K14 is similarly expressed in foetal and postnatal epidermis and its protein levels are preserved both in vivo and in vitro disease models. In this study, we focused on foetal keratins as additional KLHL24 substrates. We showed that K7, K8, K17 and K18 protein levels are markedly reduced via proteasome degradation in normal foetal keratinocytes transduced with the mutant KLHL24 protein (Delta N28-KLHL24) as compared to control cells expressing the wild-type form. In addition, heat stress led to keratin network defects and decreased resilience in Delta N28-KLHL24 cells. The KLHL24-mediated degradation of foetal keratins could contribute to congenital skin defects in EBS-KLHL24. Furthermore, we observed that primary keratinocytes from EBS-KLHL24 patients undergo accelerated clonal conversion with reduced colony forming efficiency (CFE) and early replicative senescence. Finally, our findings pointed out a reduced CFE in Delta N28-KLHL24-transduced foetal keratinocytes as compared to controls, suggesting that mutant KLHL24 contributes to patients' keratinocyte clonogenicity impairment