The article presents an annotation system for narratological phenomena such as space, time, focalisation, reported speech, narrator's speech, the relationship between the speech of a character/of the ...narrator and that of a certain character, evaluative remarks, negation, figurative speech, and ambiguity. Guidelines for annotation are being developed in order to enable different people to achieve consistent results when working with the same text (inter-annotator agreement). In doing so, narratological models will be systematically reassessed and refined. The aim of this project is therefore to annotate approximately 100 short German-language narratives. The corpus will be reusable for a variety of purposes. It permits systematic access to corpus segments annotated in the same way and supports quantifiable contributions in the fields of historical narratology, cultural studies and the history of literary genres.
Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes ...(sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort.
Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings.
Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27-0.81, P = 0.006) in a multivariate model.
IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.
U radu se analizira djelatnost znamenitoga jugoslavenskog arhitekta Milana Zlokovića (1898.-1965.) na prostoru Hrvatske u razdoblju između svjetskih ratova (1918.-1941.). Inspiriran mediteranstvom i ...modernizmom, ostavio je nekoliko natječajnih i nerealiziranih projekata, kao i dvije izvedbe u Orebiću, od kojih svi zaslužuju podrobniji historiografski osvrt. Dokumentacija koja svjedoči o Zlokovićevu radu, odnedavno dostupna u digitaliziranom obliku, pomoći će u valorizaciji njegova djela i u drugim dijelovima bivše Jugoslavije.
This paper focuses on the architectural work of Milan Zloković, the renowned Yugoslav architect (1898-1965) who worked in Croatia between the two world wars (1918-1941). Inspired by the Mediterranean style and Modernism, he left a legacy of several competition and unbuilt projects as well as two realized projects in Orebić. They deserve to be thoroughly examined from a historiographical perspective. The archives about Zloković’s work, now available in digital format, will help to evaluate his work in other parts of former Yugoslavia as well.
The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are ...operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents.
Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors. Pre-treatment biopsies and post-treatment tumor resections were analyzed by mIF (PerkinElmer Vectra) using an antibody panel that characterized tumor cells (cytokeratin-positive), immune cells (CD3, CD8, CD163, FoxP3), and PD-L1 expression. mIF estimates of sTIL score and PD-L1 expression were compared to the H&E/SP142 clinical assays. Hierarchical linear modeling was utilized to compare pre- and post-treatment immune cell expression, account for correlation of time-dependent measurement, variation across high-powered magnification views within each subject, and variation between subjects. Simulation methods (Monte Carlo, bootstrapping) were used to evaluate the impact of model and tissue sample size on statistical power.
mIF estimates of sTIL and PD-L1 expression were strongly correlated with their respective clinical assays (p < .001). Hierarchical linear modeling resulted in more precise estimates of treatment-related increases in sTIL, PD-L1, and other metrics such as CD8+ tumor nest infiltration. Statistical precision was dependent on adequate tissue sampling, with at least 15 high-powered fields recommended per specimen. Compared to conventional t-testing of means, hierarchical linear modeling was associated with substantial reductions in enrollment size required (n = 25➔n = 13) to detect the observed increases in sTIL/PD-L1.
mIF is useful for quantifying treatment-related dynamic changes in sTILs/PD-L1 and is concordant with clinical assays, but with greater precision. Hierarchical linear modeling can mitigate the effects of intratumoral heterogeneity on immune cell count estimations, allowing for more efficient detection of treatment-related pharmocodynamic effects in the context of clinical trials.
NCT02950259 .
Intertemporal choice involves deciding between smaller, sooner and larger, later rewards. People tend to prefer smaller rewards that are available earlier to larger rewards available later, a ...phenomenon referred to as temporal or delay discounting. Despite its ubiquity in human and non-human animals, temporal discounting is subject to considerable individual differences. Here, we provide a critical narrative review of this literature and make suggestions for future work. We conclude that temporal discounting is associated with key socio-economic and health-related variables. Regarding personality, large-scale studies have found steeper temporal discounting to be associated with higher levels of self-reported impulsivity and extraversion; however, effect sizes are small. Temporal discounting correlates negatively with future-oriented cognitive styles and inhibitory control, again with small effect sizes. There are consistent associations between steeper temporal discounting and lower intelligence, with effect sizes exceeding those of personality or cognitive variables, although socio-demographic moderator variables may play a role. Neuroimaging evidence of brain structural and functional correlates is not yet consistent, neither with regard to areas nor directions of effects. Finally, following early candidate gene studies, recent Genome Wide Association Study (GWAS) approaches have revealed the molecular genetic architecture of temporal discounting to be more complex than initially thought. Overall, the study of individual differences in temporal discounting is a maturing field that has produced some replicable findings. Effect sizes are small-to-medium, necessitating future hypothesis-driven work that prioritizes large samples with adequate power calculations. More research is also needed regarding the neural origins of individual differences in temporal discounting as well as the mediating neural mechanisms of associations of temporal discounting with personality and cognitive variables.
Centrioles function in the assembly of centrosomes and cilia. Structural and numerical centrosome aberrations have long been implicated in cancer, and more recent genetic evidence directly links ...centrosomal proteins to the etiology of ciliopathies, dwarfism and microcephaly. To better understand these disease connections, it will be important to elucidate the biogenesis of centrioles as well as the controls that govern centriole duplication during the cell cycle. Moreover, it remains to be fully understood how these organelles organize a variety of dynamic microtubule-based structures in response to different physiological conditions. In proliferating cells, centrosomes are crucial for the assembly of microtubule arrays, including mitotic spindles, whereas in quiescent cells centrioles function as basal bodies in the formation of ciliary axonemes. In this short review, we briefly introduce the key gene products required for centriole duplication. Then we discuss recent findings on the centriole duplication factor STIL that point to centrosome amplification as a potential root cause for primary microcephaly in humans. We also present recent data on the role of a disease-related centriole-associated protein complex, Cep164-TTBK2, in ciliogenesis.
Streak tube imaging lidar (STIL) is an active imaging system that has a high range accuracy and a wide range gate with the use of a pulsed laser transmitter and streak tube receiver to produce 3D ...range images. This work investigates the range accuracy performance of STIL systems based on a peak detection algorithm, taking into account the effects of blurring of the image. A theoretical model of the time-resolved signal distribution, including the static blurring width in addition to the laser pulse width, is presented, resulting in a modified range accuracy analysis. The model indicates that the static blurring width has a significant effect on the range accuracy, which is validated by both the simulation and experimental results. By using the optimal static blurring width, the range accuracies are enhanced in both indoor and outdoor experiments, with a stand-off distance of 10m and 1700m, respectively, and corresponding, best range errors of 0.06m and 0.25m were achieved in a daylight environment.
•A theoretical model of time-resolved signal distribution including both the static blurring width and laser pulse width is presented.•The relationship between range accuracy and static blurring width is analyzed, and is validated by both simulation and experimental results•By using the optimal static blurring width, the range accuracies have been enhanced in both indoor and outdoor experiments with a stand-off distance of 10m and 1700m, respectively.•The work presented here is useful for the design and evaluation of the STIL systems.
Cilj je ovoga rada bio ispitati međugeneracijske učinke kognitivnoga stila obilježenoga strepnjom majki i njihovih ponašanja na razvoj anksioznosti i depresivnosti djece. Kognitivni stil obilježen ...strepnjom označava tendenciju pojedinca da generira dinamične mentalne scenarije u kojima se prijetnja povećava i približava. Istraživanja ukazuju na povezanost toga stila i anksioznosti. S obzirom na nekonzistentnost u povezivanju toga stila i depresije, pokušali su se definirati uvjeti pod kojima se ta povezanost pojavljuje uvođenjem moderatorske varijable stresnih životnih događaja. Istraživanje je provedeno na 126 parova majki i djece. Rezultati potvrđuju hipotezu da kognitivni stil majke obilježen strepnjom ima doprinos u međugeneracijskome prijenosu anksioznosti, ali sugeriraju i njegov doprinos u objašnjenju depresivnosti. Djeca majki koje su imale izraženiji kognitivni stil obilježen strepnjom imala su višu razinu anksioznosti i depresivnosti. Roditeljska ponašanja koja uključuju modeliranje i verbalni prijenos informacija o prijetnji značajno predviđaju pojavu anksioznosti kod djece. Utvrđen potpuni medijacijski efekt upućuje na to da kognitivni stil obilježen strepnjom majki ima značajan efekt na anksioznost djece samo putem modeliranja majki te je utvrđen i medijacijski efekt modeliranja majki u odnosu kognitivnoga stila obilježenoga strepnjom majki i depresivnosti kod djece. Moderatorski efekt stresnih životnih događaja u odnosu kognitivnoga stila obilježenoga strepnjom majki i depresivnosti njihove djece nije potvrđen. Dobiveni rezultati ukazuju na važnost roditeljskih ponašanja u objašnjenju simptoma anksioznosti i depresivnosti kod djece.
Istraživanja kontinuirano pokazuju da interes, motivacija i uključenost u učenje fizike opadaju s godinama školovanja. Neka istraživanja pokazuju i da pad interesa za učenje fizike započinje već na ...početku formalnoga obrazovanja iz fizike pa je cilj ovoga istraživanja bio ispitati odrednice motivacije i uključenosti u učenje učenika koji se prvi put susreću s predmetom fizike. Uključenost u učenje predstavlja opažljivu manifestaciju motivacije, a većina autora smatra da je sačinjavaju bihevioralni (pažnja, koncentracija i ustrajnost), kognitivni (učenje s razumijevanjem) i emocionalni (pozitivne emocije za vrijeme učenja) aspekt. Za teorijski okvir odabran je kontekstualni model školske uključenosti prema kojemu motivacijska uvjerenja učenika posreduju u odnosu između kontekstualnih čimbenika i uključenosti. U istraživanju je sudjelovalo 595 učenika sedmih razreda iz deset osnovnih škola u Zagrebu prosječne dobi od 13 godina (51 % djevojčica). Za provjeru medijatorne uloge motivacijskih uvjerenja učenika (samoefikasnosti, interesa, važnosti i korisnosti fizike) u odnosu između triju aspekata motiviranja učenika (nastavnička brižnost, poticanje autonomije i nastavnička struktura) te triju aspekata uključenosti u učenje (bihevioralnoga, kognitivnoga i emocionalnoga) korišteno je strukturalno modeliranje. Rezultati istraživanja u skladu su s teorijskim modelom i pokazali su da tri aspekta uključenosti u učenje fizike imaju različite mehanizme na početku formalnoga obrazovanja iz fizike. Najvažnijim se medijatorom pokazao interes za fiziku koji je posredovao u odnosu između nastavničke brižnosti i strukture te bihevioralne i emocionalne uključenosti u učenje fizike, dok su uvjerenja o samoefikasnosti i korisnosti fizike posredovala u odnosu između nastavničkoga poticanja autonomije te kognitivne uključenosti u učenje fizike. Rezultati imaju teorijske i praktične implikacije.
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