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Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance

This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03−2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12−3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.Carmela Ricciardelli, Noor A Lokman, Carmen E Pyragius, Miranda P Ween, Anne M Macpherson, Andrew Ruszkiewicz, Peter Hoffmann, Martin K Oehle

Prosochê i przeobrażenie siebie w poezji Geoffreya Chaucera

The article deals with the concept of prosochê, defined as concentration on the present moment, in Geoffrey Chaucer’s poetry. Even though the Greek term never appears in Chaucer’s poetry, the idea of attentive reflection on the self, others, and the cosmos is often articulated by the poet, especially in his courtly poetry, which construes individuals as steeped in apathy and in need of inner transformation. The poet underlines the transformative power of attention through a call to wake up, examples of which will be examined in this article, based on two poems: The Book of the Duchess and Troilus and Criseyde. It will be shown that Chaucer’s engagement with the concept of prosochê is testament to the poet’s creativity while handling his sources as well as to his moral sensitivity and philosophical reflection.Tematem niniejszego artykułu jest pojęcie prosochê, definiowane jako skupienie się na chwili obecnej, w poezji Geoffreya Chaucera. Mimo iż sam termin grecki nie pojawia się w utworach Chaucera, to idea uważnej refleksji nad samym sobą, innymi oraz kosmosem jest mocno zaakcentowana przez angielskiego poetę, szczególnie w jego poezji dworskiej, która przedstawia postaci pogrążone w apatii oraz potrzebujące wewnętrznej przemiany. Poeta podkreśla transformacyjną moc uwagi poprzez wezwanie do przebudzenia, którego przykłady zostaną omówione w niniejszym artykule na podstawie dwóch utworów: Księga księżnej oraz Troilus i Criseyda. To, w jaki sposób poeta&nbsp;traktuje temat prosochê, świadczy o jego twórczym podejściu do źródeł, jak również o wrażliwości moralnej i filozoficznej refleksji

“Be war in tyme, approchis neir the end”: The sense of an ending in "The Testament of Cresseid"

The story of Troilus and Criseyde – whether in Chaucer’s or Henryson’s renditions – is not a story about a new beginning, but a story about an end: the end of love, of hope, and finally – the end of life: Troilus’s life in Chaucer’s poem and Cresseid’s life in Henryson’s. The Scottish version of the story, however, not only evokes the end of an individual life, but also the end of the world. The purpose of this paper is to situate Henryson’s poem in the context of apocalyptic fiction – fiction which is concerned with loss, decay and the finality of things. My contention that the poem belongs to the apocalyptic genre is based on a number of its features, such as the elegiac mood and imagery, the contrast between the past and the present, as well as the pattern of sin-redemption-preparation for death, which applies to Cresseid’s life, but also invites reflection on our own

Evaluation of Thermal Mechanisms to Predict the Transient Electroplastic Effect in Aluminum and an Investigation of Electrically Assisted Drilling

The objective of this research is twofold: first, to evaluate if the microscale Joule heating theory can predict the transient electroplastic effect in 7075-T6 aluminum. Second, to determine if electrical application can have a significant impact on drilling of 1500MPa steel, and if the operation is predictable using a modified Merchant’s machining model. Both 7075-T6 and 1500 MPa steel are of interest to the automotive industry due to their high strength-to-weight ratios. These metals are important to aid in lightweighting to meet increasingly strict governmental fuel economy standards. However, the strength of the steel makes it difficult to machine in post-forming operations. The ductility of the aluminum makes it impossible to form using conventional methods, especially for deep parts such as a body side outer. A potential fix to these problems is electrical augmentation to locally or globally soften the metal. It has been shown that electricity can increase ductility/formability in metals while also decreasing the forming loads and stresses required (this group of phenomena is termed the electroplastic effect). While the effects of electricity are well known, the underlying mechanisms are not, resulting in four key theories, two of which have already been disproven. This research examines one of the remaining two theories to predict the transient electroplastic effect. The microscale Joule heating theory suggests that microscale hot spots develop inside of the metal in areas of high electrical resistivity, such as grain boundaries where dislocations pile up during deformation. A coupled mechanical-thermal-electrical model was partitioned with grains, grain boundaries, and precipitates. Temperature and dislocation density-dependent electrical resistivity was used in order to evaluate the microscale Joule heating theory. It was found that this theory cannot fully explain the resultant stress drop caused during the transient phase of electrically-assisted pulsed tension. During model testing it was discovered that electricity changes the strain hardening behavior of aluminum. To further investigate, the effect of electricity on precipitates was explored through measurement of precipitate size and distribution in specimens treated with different electrical treatments. An electrically-assisted drilling experiment was designed, fabricated, and tested to determine the effect of electricity on a drilling process. A design of experiments study was conducted on 1008 steel to determine if electric current had a significant effect on process temperature, axial force, and tool wear compared to inputs of feedrate and spindle RPM. It was found that current was dominant and that tool wear and cutting forces could be decreased with electric current. The first electrically-assisted drilling model was created by modifying Merchant’s machining model. This model was found to have shortcomings due to knowledge limitations on friction and equipment limitations on temperature measurement. The knowledge generated from the 1008 experiments was used to further the constraining limits of the drilling process, leading to 1000% tool life improvement on drilling of 1500 MPa steel while increasing the achievable feedrate for cutting by 200%

The secret life of small alcohols: the discovery and exploitation of fragmentation, adduct formation and auto-modification phenomena in differential ion mobility spectrometry leading to next-generation toxicity screening

The research presented in this thesis started with the idea to study alcohols as modifiers and dopants in differential ion mobility spectrometry (d-IMS) to produce complicated chemical signatures to explore a concept of chemical labels for product security application. D-IMS is a gas phase atmospheric pressure separation and detection technique which distinguishes compounds based on differences in their ions mobility as their travel under a low and high electric field. The hypothesis was that alcohols will form typical d-IMS products such as protonated monomers and proton bound cluster ions. However, the very first experiments revealed unexpected phenomena which included changes in the mobility of ions over a narrow range of concentrations that could not be explained by existing theory. Another observation was the apparent regeneration of reactant ions. It became evident that the observed phenomena had not been described in the open literature and that addressing the research-questions that were being raised would be essential for the determination of alcohols by d-IMS and its use in medical applications for toxicity screening and monitoring of alcohols. The above discovery shifted the research objective towards a fundamental and comprehensive study on the behaviour of alcohols in d-IMS. This thesis describes designed experiments and constructed systems allowing the efficient study of effect of concentration, electric field and temperature on the d-IMS responses of alcohols. The results of those studies demonstate: extensive fragmentation of alcohols, including previously undescribed fragmentation patterns with regeneration of the hydrated proton; new phenomena of adduct ion formation within the d-IMS drift tube, observed in the case of methanol within a narrow range of concentration; and self-modification of the alpha function of alcohols. This knowledge was exploited by developing an non-invasive analytical method for recovery, separation and detection of toxins from human saliva (including alcohols, diols and GHB) using TD-GC-d-IMS (thermal desorption - gas chromatography d-IMS) within a full range of toxicological concentration levels

Glycaemic control and awareness among diabetic patients of nutrition recommendations in diabetes

Wprowadzenie. Zapadalność na cukrzycę szybko wzrasta, szczególnie w krajach zurbanizowanych. Szacuje się, że w skali całego świata do 2035 r. liczba chorych na cukrzycę osiągnie poziom 600 milionów. Jest coraz więcej dowodów na to, że odpowiednia edukacja pacjentów jest jednym z najskuteczniejszych sposobów na opóźnienie rozwoju powikłań. Cel. Celem badań była ocena częstości wykonywania przez pacjentów pomiarów glikemii oraz ich wiedzy na temat zaleceń żywieniowych w cukrzycy. Materiał i metody. Badanie objęło grupę 303 pacjentów z cukrzycą typu 1 i 2. Narzędziem badawczym była autorska ankieta wzorowana na kwestionariuszu KomPAN, która składała się z testu wiedzy oraz pytań dotyczących samokontroli glikemii. Analizy statystycznej dokonano za pomocą programu PS IMAGO PRO 5 (IBM SPSS Statistics 25). Wyniki. Większość pacjentów wykazała się średnim poziomem wiedzy żywieniowej – 62% z nich uzyskało >50% poprawnych odpowiedzi. Jedynie 8% respondentów uzyskało wynik >80% punktów. Lepsze wyniki z testu uzyskiwali pacjenci z cukrzycą typu 1. Najwyższy odsetek poprawnych odpowiedzi uzyskano w pytaniach o konieczność eliminowania słodyczy i wprowadzenia do diety bogatych w błonnik pełnoziarnistych produktów zbożowych (>90% poprawnych odpowiedzi), a najniższy odsetek zaobserwowano w pytaniach wymagających oszacowania węglowodanów prostych i indeksu glikemicznego konkretnych produktów (<30% poprawnych odpowiedzi). Większość pacjentów wykonywała pomiar glikemii przynajmniej raz dziennie, jednak 6% zaniechało pomiarów domowych. Prawie połowa respondentów nie miała wykonywanego testu hemoglobiny glikowanej - większość tej grupy stanowili pacjenci z cukrzycą typu 2. Wnioski. Poziom wiedzy badanych pacjentów był niezadowalający i różnił się w zależności od typu cukrzycy. Potrzebna jest dalsza edukacja pacjentów w zakresie żywienia i samokontroli glikemii.Background. The incidence of diabetes has been rising rapidly, especially in urbanized countries. It is estimated that by 2035 the number of diabetics will have increased to almost 600 million around the world. There is a substantial amount of evidence which points to proper education as one of the most effective ways of delaying the diabetes-related development of complications. Objective. The aim of the study was to investigate the frequency of monitoring blood sugar by diabetic patients and their awareness of nutrition recommendations in diabetes. Materials and methods. The study included 303 patients with type 1 and 2 diabetes. The research tool was a questionnaire based on the KomPAN questionnaire that consisted of a nutrition knowledge test and several questions concerning glycaemic control. The statistical analysis was carried out using the PS IMAGO PRO 5 (IBM SPSS Statistics 25) software. Results. Most of the patients demonstrated a medium level of knowledge – 62% of them provided >50% of the correct answers. Only 8% of the respondents scored >80% of the correct answers. Better test results were achieved by patients with type 1 diabetes. The highest percentage of correct answers was observed in the questions regarding the need to limit sweets or introduce fibre-rich whole-grain products (>90%), the smallest percentage in the questions related to the assessment of carbohydrates and the glycaemic index of selected products (<30%). The majority of the patients checked their blood sugar levels every day, but 6% of them gave up glucose measurements at home. About half of the respondents did not take the HbA1c test - the majority of them were patients with type 2 diabetes. Conclusions. The level of knowledge of the examined patients was unsatisfactory and varied with the type of diabetes. Further education of patients about nutrition and glycaemic control is recommended

Some interesting species of the genus Ascochyta

The paper presents eleven species of Ascochyta recently collected in central and southern part of Poland. Two of them, Ascochyta bondarceviana Melnik and Ascochyta equiseti (Desm.) Grove noted in Poland for the first time, are illustrated with microphotographs. In addition, nine other species are newly reported on their host plants species in the country. Short characteristics of the fungi species based on the collected specimens and the distribution maps of all fungi taxa are presented

The genus Fusicladium (Hyphomycetes) in Poland

The paper presents new and historical data on the genus Fusicladium verified on the base of the recently published critical monograph. Fifteen species recorded in Poland under the name Fusicladium and synonymous Pollaccia and Spilocaea are reported; 5 are documented by authors’ materials from Central Poland while the other taxa are supported with literature data only, including three species belonging currently to Fusicladiella and Passalora. Three species, reported here for the first time in Poland: Fusicladium convolvularum Ondřej, F. scribnerianum (Cavara) M. B. Ellis and F. virgaureae Ondřej, are known from a few localities in the world. All the species are provided with the distribution maps and the newly reported ones are illustrated with ink drawings

Can we accurately report PTEN status in advanced colorectal cancer?

BACKGROUND: Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results. METHODS: We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed. RESULTS: Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%). CONCLUSION: Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer