Translation Hypothesis Research Articles

Application of translation technology based on AI in translation teaching

Nowadays, translation technology based on artificial intelligence (AI) has gradually matured. Traditional translation teaching methods have many limitations, such as time and space limitations, increased labor costs, etc. In this context, this article explored the application of translation technology based on AI in translation teaching. In this paper, neural machine translation (NMT) algorithm was used to encode and decode the original text to generate the corresponding translation. The statistical machine translation (SMT) algorithm was used to build the translation model, which was based on the statistical model. The algorithm searched for the best translation hypothesis through inference, which can improve the accuracy and readability of translation. Compared with traditional machine translation (MT), the accuracy rate of AI based translation in this paper reached 97 %, which was far higher than traditional MT and more suitable for teaching. The improvement in student translation was also relatively obvious, which can be clearly seen through students’ translation test scores. At the same time, the teacher's satisfaction with the AI translation teaching system in this article was also high, with an average score of 92 points. Through the application research of translation technology based on AI in translation teaching, AI translation teaching has a positive promoting effect on improving students’ translation level and efficiency.

The influences of familiarity and key on pitch accuracy in singing

Singing is a typical human behavior but individuals vary in pitch accuracy. Poor singing performance can be explained by deficits in translating sensory information to a vocal motor plan or problems encoding or recalling pitch from long-term memory. We compared the sensorimotor translation and long-term memory hypotheses by assessing the influence of familiarity and musical key on singing performance. Thirty participants imitated excerpts of 20 familiar and unfamiliar pop songs presented in their original key or a transposed key. We analyzed pitch accuracy by measuring the difference in pitch between the first two notes of participants’ productions and the target stimuli. Participants sang familiar songs more accurately than unfamiliar songs and songs in their original keys less accurately than songs in transposed keys. The results, based on Bayesian hypothesis testing, provide some support for both memory hypotheses and partially confirm the findings of previous research on singing performance. Importantly, our work suggests that if individuals maintain pitch information in long-term memory, they do not draw on it when imitating songs.

Who's afraid of false friends? Cognate ratios in translated and non-translated Dutch

AbstractThis paper presents an empirical study on the proportion of cognate words (cognate ratios) in translated Dutch texts, compared to cognate words ratio in texts originally written in Dutch. To this end, we compiled a gold standard with manually verified cognate pairs for both studied language pairs, viz. English–Dutch and French–Dutch. In this study, we propose three hypotheses about how translators deal with cognates: (1) translators use the high degree of formal and semantic overlap between cognate translations to their advantage so as to produce the “easiest and fastest” translation (default translation hypothesis), (2) the higher the level of cognateness between a source and target language, the higher the cognate ratio in translated texts will be (cognate facilitation effect), (3) the higher the level of cognateness between the two languages, the more translators will be hesitant to use cognate translations (fear of false friends hypothesis). The results show a mixed picture: whereas not much evidence has been found for the first two hypotheses (depending on the respective language pair), the third hypothesis was confirmed. Further evidence, however, is needed from other language pairs, as cognate-receptiveness appears to be language-specific.

Analysis of ‘Heart’ Metaphors in the Translation of To The Lighthouse: A Cognitive-Inspired Approach

Metaphors as a matter of thought can differ across languages and cultures depending on life experience, cultural background and individual differences. Emotion-related metaphors are widely used specifically in literary texts for conveying certain effects. Translating emotion-related metaphors can be a hard task, as problems arise due to differences between two conceptual systems. Several researchers have highlighted the importance of Conceptual Metaphor Theory (CMT) for understanding and analyzing metaphors. This study aims to analyze emotion-related metaphors, particularly the ‘heart’ metaphors extracted from the novel To The Lighthouse and their translation into Arabic. In the analysis, the researchers identified the underlying conceptual metaphor of each metaphorical expression and looked at how it was expressed at the linguistic level. The conceptual metaphors of the source text (ST) and the target text (TT) were then categorized considering the Cognitive Translation Hypothesis (CTH). The findings indicate that ‘heart’ metaphors were used similarly at the conceptual level in both languages, but in some cases, they differed slightly at the linguistic level. This confirms the basic premise that some emotion-related concepts are universal and deeply rooted in our thought and cognition. The translator used the strategy of addition mostly to produce a plausible equivalent. Moreover, it was found that ‘heart’ occurred more frequently in the Arabic translation of the novel in which metaphorization was used to express emotions in the ST even if ‘heart’ was not used in the expression.

Preferred synonymous codons are translated more accurately: Proteomic evidence, among-species variation, and mechanistic basis.

A commonly stated cause of unequal uses of synonymous codons is their differential translational accuracies. A key prediction of this long-standing translational accuracy hypothesis (TAH) of codon usage bias is higher translational accuracies of more frequently used synonymous codons, which, however, has had no direct evidence beyond case studies. Analyzing proteomic data from Escherichia coli, we present direct, global evidence for this prediction. The experimentally measured codon-specific translational accuracies validate a sequence-based proxy; this proxy provides support for the TAH from the vast majority of over 1000 taxa surveyed in all domains of life. We find that the relative translational accuracies of synonymous codons vary substantially among taxa and are strongly correlated with the amounts of cognate transfer RNAs (tRNAs) relative to those of near-cognate tRNAs. These and other observations suggest a model in which selections for translational efficiency and accuracy drive codon usage bias and its coevolution with the tRNA pool.

Looking under the Hood for Evidence of Normalization

The study investigated the hypothesis of normalization and stylistic variation across translators as manifested in the use of lexical bundles between translated and non-translated English literary texts. Normalization is a hypothesis originally proposed as ‘conservatism’ by Baker (1996) which states that the translator tends to conform to linguistic patterns and conventions typical of the target language even to the point of exaggeration, and lexical bundles are sequences of three or four words recurring with high frequency in natural discourse. The study was carried out in two stages. The first stage replicated previous studies that relied on simple frequency tests to confirm the normalization hypothesis. Contrary to these earlier studies, the present study’s frequency tests on lexical bundles failed to provide clear support for the normalization hypothesis. The second stage employed two types of multivariate exploratory analysis, principal component analysis (PCA) and hierarchical cluster analysis (HCA), to examine the underlying relationships among individual texts, lexical bundles, and translated and non-translated group categories. Following the failed frequency tests, it was hypothesized here that normalization might be still present in the translated corpus but restricted by types of lexical bundles. PCA confirmed this hypothesis by revealing that normalization occurred in the use of a particular functional type of lexical bundles, called discourse bundles, which are relatively free from the thematic content of the text in which they occur. This ascertains the traditional idea that statistical tests of translation hypotheses must deal with linguistic features unrelated to the thematic content of the corpus. Additionally, PCA revealed variation across the types of lexical bundles preferred by individual translators. HCA further identified the presence of a subgroup of translated texts that cluster with non-translated texts, rather than with their fellow translated texts. This was taken as indicating that the use of lexical bundles varied among the translators and that the division between translated and non-translated texts is not clear-cut.

Methylphenidate as a causal test of translational and basic neural coding hypotheses

Most systems neuroscience studies fall into one of two categories: basic science work aimed at understanding the relationship between neurons and behavior, or translational work aimed at developing treatments for neuropsychiatric disorders. Here we use these two approaches to inform and enhance each other. Our study both tests hypotheses about basic science neural coding principles and elucidates the neuronal mechanisms underlying clinically relevant behavioral effects of systemically administered methylphenidate (Ritalin). We discovered that orally administered methylphenidate, used clinically to treat attention deficit hyperactivity disorder (ADHD) and generally to enhance cognition, increases spatially selective visual attention, enhancing visual performance at only the attended location. Further, we found that this causal manipulation enhances vision in rhesus macaques specifically when it decreases the mean correlated variability of neurons in visual area V4. Our findings demonstrate that the visual system is a platform for understanding the neural underpinnings of both complex cognitive processes (basic science) and neuropsychiatric disorders (translation). Addressing basic science hypotheses, our results are consistent with a scenario in which methylphenidate has cognitively specific effects by working through naturally selective cognitive mechanisms. Clinically, our findings suggest that the often staggeringly specific symptoms of neuropsychiatric disorders may be caused and treated by leveraging general mechanisms.

Mosaic translation hypothesis: chimeric polypeptides produced via multiple ribosomal frameshifting as a basis for adaptability.

How many different proteins can be produced from a single spliced transcript? Genome annotation projects overlook the coding potential of reading frames other than that of the reference open reading frames (refORFs). Recently, alternative open reading frames (altORFs) and their translational products, alternative proteins, have been shown to carry out important functions in various organisms. AltORFs overlapping refORFs or other altORFs in a different reading frame may be involved in one fundamental mechanism so far overlooked. A few years ago, it was proposed that altORFs may act as building blocks for chimeric (mosaic) polypeptides, which are produced via multiple ribosomal frameshifting events from a single mature transcript. We adopt terminology from that earlier discussion and call this mechanism mosaic translation. This way of extracting and combining genetic information may significantly increase proteome diversity. Thus, we hypothesize that this mechanism may have contributed to the flexibility and adaptability of organisms to a variety of environmental conditions. Specialized ribosomes acting as sensors probably played a central role in this process. Importantly, mosaic translation may be the main source of protein diversity in genomes that lack alternative splicing. The idea of mosaic translation is a testable hypothesis, although its direct demonstration is challenging. Should mosaic translation occur, we would currently highly underestimate the complexity of translation mechanisms and thus the proteome.

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.

Abstract 212: Sarcoma-CellMiner: An extensive resource for patient-derived sarcoma cell line epigenetics, genomics and pharmacology

Abstract Sarcomas represent a heterogeneous group of cancers with many histological subtypes. Their prognosis remains poor and treatment is mainly based on palliative chemotherapy at metastatic stage. Tumor genome sequencing failed to identify recurrent somatic drivers while several oncogenic gene fusion-translocations have been identified in specific sarcoma subtypes. Because of the rarity and heterogeneity of sarcomas, only few sarcoma patients are enrolled in clinicals trials according their subtype. Increased translational research according subtypes of sarcoma patients is needed to improve patient management. To characterize the differences between subgroups and build translational hypotheses, we built a novel resource, Sarcoma-Cellminer, which integrates drug sensitivity and genomic data from 112 patient-derived sarcoma cell lines. These data will be available from a web-based tool (https://discover.nci.nih.gov/SclcCellMinerCDB/) derived from our CellMiner cross-database web application (https://discover.nci.nih.gov/cellminercdb). Among the 112 cell lines, 65 are bone sarcomas (including 38 Ewing sarcomas and 22 osteosarcomas), 45 are soft tissue sarcomas (including 21 rhabdomyosarcomas). Transcriptome (RNAseq and microarray), copy number, microRNA, genome-wide methylation, and drug sensitivity data are included and made publicly available. We also generated new genomic data including copy number and methylation (850 k) for 79 cell lines from the NCI in addition to the 42 cell lines from Broad Institute (CCLE) and the 40 cell lines from the MGH-Sanger (GDSC). We created the “SCLC-Global” expression set by regrouping all datasets by Z-score normalization, which enables cross-database analyses of gene expression and molecular pathways. Hierarchical clustering based on expression and methylation data identifies subtypes of sarcomas. Histone genes stand out suggesting that epigenetic regulation of canonical histones is a feature of sarcoma genesis. Sarcoma-CellMiner includes drug sensitivity data for over 500 different drugs tested in the NCI, CCLE and GDSC databases. They show two subgroups of Ewing sarcomas: one sensitive to PARP inhibitors and one resistant. Similarly, profile of response to dasatinib is different when comparing alveolar and embryonal rhabdomyosarcomas. Sarcoma-CellMiner is a powerful tool demonstrating the value of patient-derived cancer cell line databases. It provides hypothesis-driven rationale for using omics, especially transcriptome and epigenetic data to better understand sarcoma heterogeneity and select personalized treatments for clinical trials. Citation Format: Camille Tlemsani, Lorinc Pongor, Javed Khan, Fathi Elloumi, Sudhir Varma, Augustin Luna, Vinodh Rajapakse, Kurt Kohn, Julia Krushkal, Mirit Aladjem, Beverly Teicher, Paul Meltzer, William Reinhold, Christine Heske, Yves Pommier. Sarcoma-CellMiner: An extensive resource for patient-derived sarcoma cell line epigenetics, genomics and pharmacology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 212.

Detection of H3K4me3 Identifies NeuroHIV Signatures, Genomic Effects of Methamphetamine and Addiction Pathways in Postmortem HIV+ Brain Specimens that Are Not Amenable to Transcriptome Analysis.

Human postmortem specimens are extremely valuable resources for investigating translational hypotheses. Tissue repositories collect clinically assessed specimens from people with and without HIV, including age, viral load, treatments, substance use patterns and cognitive functions. One challenge is the limited number of specimens suitable for transcriptional studies, mainly due to poor RNA quality resulting from long postmortem intervals. We hypothesized that epigenomic signatures would be more stable than RNA for assessing global changes associated with outcomes of interest. We found that H3K27Ac or RNA Polymerase (Pol) were not consistently detected by Chromatin Immunoprecipitation (ChIP), while the enhancer H3K4me3 histone modification was abundant and stable up to the 72 h postmortem. We tested our ability to use H3K4me3 in human prefrontal cortex from HIV+ individuals meeting criteria for methamphetamine use disorder or not (Meth +/−) which exhibited poor RNA quality and were not suitable for transcriptional profiling. Systems strategies that are typically used in transcriptional metadata were applied to H3K4me3 peaks revealing consistent genomic activity differences in regions where addiction and neuronal synapses pathway genes are represented, including genes of the dopaminergic system, as well as inflammatory pathways. The resulting comparisons mirrored previously observed effects of Meth on suppressing gene expression and provided insights on neurological processes affected by Meth. The results suggested that H3K4me3 detection in chromatin may reflect transcriptional patterns, thus providing opportunities for analysis of larger numbers of specimens from cases with substance use and neurological deficits. In conclusion, the detection of H3K4me3 in isolated chromatin can be an alternative to transcriptome strategies to increase the power of association using specimens with long postmortem intervals and low RNA quality.

Translation hypothesis specifics and problems of translation of scientific and technical multi component terms

In this article highlights of translation hypothesis. specifics and problems of translation of scientific and technical multicomponent terms. We divide it into two components: the total power and the directed rays. One of the most effective methods for testing a hypothesis is a search engine on the Internet. The dictionary includes only a limited set of values in each zone: not everything that is in the language, but only what may be needed for automatic processing of highly specialized texts and makes this processing less complex. In order to translate them correctly, you need to understand how the keywords are expressed in these terms. We see that all of them have a suffix-n, which most likely indicates that they belong to the verbal forms of the noun.

Literal translation in the light of the gravitational pull hypothesis: The case of sentence-initial indefinite noun phrases in singular in Norwegian-to-German and German-to-Norwegian translation

The present article reports on a study of renditions of sentence-initial indefinite noun phrases (NPs) in singular in Norwegian-to-German and German-to-Norwegian parallel corpus data. It briefly describes the correspondences to such NPs and the translation- induced changes that are made in the structure of the sentences including the phrase. In particular, however, the study focuses on fully congruent correspondences to singular sentence-initial indefinite NPs, i. e., the instances in which the structure is formally copied in translational renditions. Finding out to what extent such sentence initials are preserved in translation allows us to verify the hypothesis about literal translation that pertains to a potential (yet somehow forgotten) translation universal. By referring the conducted study to the framework of the current version of the gravitational pull hypothesis by Sandra Halverson, it becomes possible to position the phenomenon of literal translation in the context of the latest research into bilingual cognition and to find common ground where more traditional contrastive linguistics and translation studies may meet. The analysis generally supports the literal translation hypothesis as the NPs under investigation (classified as highly salient linguistic structures) have been translated into German and Norwegian literally in over 70 %. Thus, the gravitational pull of the source text structures on the target language is of similar strength. On the other hand, it has been observed that Norwegian is more resistant to using sentence-initial indefinite NPs than German, or that German applies this way of content construal more willingly. In a broader perspective, the research results shed new light on the extent to which the linguistic patterns of the use of the indefinite article in a real text production are similar and entrenched in a bilingual’s Norwegian/German representation.

Interference in Translation and Simultaneous Interpreting from Italian into English. An Intermodal Analysis of English Genitives in the European Parliament Interpreting Corpus

This article illustrates an intermodal study on simultaneous interpreting and translation from Italian into English based primarily on the European Parliament Interpreting Corpus (EPIC) and official translations from the European Parliament. In line with Gideon Toury’s posited law of interference, the hypothesis that drives the present study is that interpreters and translators working into English from Italian may underrepresent the ’s-genitive as a result of the syntactic asymmetry between English (which alternates between ’s and of) and Italian (which only has one type of prepositional phrase consisting of di + noun). The results of this study indicate that ’s-genitives occur with lower frequency in interpreted English than in non-mediated English, thus revealing a particular form of syntactic interference. The same tendency, however, is not found in translations from Italian into English. This difference is explained by recourse to Englund Dimitrova’s (2005) findings on translation expertise and to the literal translation hypothesis (Chesterman 2011) and by suggesting that simultaneous interpreting tends to adhere to the source-language syntax more closely than translation, thus displaying similarities with translation drafts. The results also point to the theoretical and methodological limitations of the théorie du sens developed by the Paris School of Interpreters and Translators.

CanSAR: update to the cancer translational research and drug discovery knowledgebase.

canSAR (http://cansar.icr.ac.uk) is the largest, public, freely available, integrative translational research and drug discovery knowledgebase for oncology. canSAR integrates vast multidisciplinary data from across genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and more. It also provides unique data, curation and annotation and crucially, AI-informed target assessment for drug discovery. canSAR is widely used internationally by academia and industry. Here we describe significant developments and enhancements to the data, web interface and infrastructure of canSAR in the form of the new implementation of the system: canSARblack. We demonstrate new functionality in aiding translation hypothesis generation and experimental design, and show how canSAR can be adapted and utilised outside oncology.

Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross-disciplinary translational hypothesis.

Pre‐biopsy multiparametric magnetic resonance imaging (mpMRI) has transformed the risk stratification and diagnostic approach for suspected prostate cancer. The majority of clinically significant prostate cancers are visible on pre‐biopsy mpMRI, however, there are a subset of significant tumors that are not detected by mpMRI. The radiobiological mechanisms underpinning mpMRI‐visibility and invisibility of these cancers remain uncertain. Emerging evidence suggests that mpMRI‐visible tumors are enriched with molecular features associated with increased disease aggressivity and poor clinical prognosis, which is supported by short‐term endpoints, such as biochemical recurrence following surgery. Furthermore, at the histopathological level, mpMRI‐visible tumors appear to exhibit increased architectural and vascular density compared to mpMRI‐invisible disease. It seems probable that the genomic, pathological, radiological, and clinical features of mpMRI‐visible and mpMRI‐invisible prostate cancers are interrelated. Here, we propose a novel cross‐disciplinary theory that links genomic and molecular evidence with cellular and histopathological appearances, elucidating both the mpMRI visibility and clinical status of significant prostate cancer.

The english translation of Grazia Deledda’s La Madre and the relevance of culture in translating Landscape metaphor

Este artigo explora o impacto da estrutura cultural do tradutor na tradução da metáfora relacionada à paisagem por meio de uma análise contrastiva de La madre, de Grazia Deledda, Prêmio Nobel de Literatura, e a tradução de 1922, The Mother, realizada por Mary Steegman. A cultura influencia a visão da natureza ao fornecer normas e ideologias distintas sobre como as pessoas se relacionam com os outros e com o mundo natural. A linguagem do espaço de Deledda se originou de uma percepção subjetiva, assim como seu uso de metáforas relacionadas ao espaço. Na tradução, no entanto, a negociação de significado envolvendo metáforas da paisagem se torna mais complexa. A percepção subjetiva e a individualidade do autor do original se sobrepõem à subjetividade do tradutor, que impacta o texto de chegada com consequências políticas e ideológicas. Esta contribuição examina em particular o antropomorfismo e a relação entre metáfora e símile. Argumentar-se-á que a interpretação do tradutor pode remodelar o relacionamento e a compreensão dos leitores-alvo desse cenário. A análise será baseada na teoria conceitual de metáfora e na hipótese de tradução cognitiva de Mandelblit (1995). A ecoestilística fornecerá uma estrutura adicional para examinar os padrões que revelam a abordagem do tradutor em relação à natureza e paisagem.

Research Report: The Rock of the Dead: new “Latin” or “Iberian-Guanche” Inscriptions found in Tenerife (Canary Islands, Spain)

A new panel of “Latin” or Iberian-Guanche rock inscriptions has been found in Tenerife, a transcription and translation hypotheses have been put forward based on a methodology involving semantics and phonology of Basque and ancient Iberian language (used during the 1st millennium BC in Iberia and France). Both Iberian-Guanche (at Canary Is) and Iberian (at France and Iberia) rock scripts are sometimes found together with naviform lines. These incise lineal rock scripts have been found in all Canary Islands and it supports the existence of a prehistoric Guanche common culture before Punic/Roman influence could arrive to the Archipelago and postulated Guanche incapacity to navigate is doubtful. This common writing in Canary Islands together with the finding of big rock carved (“Quesera”/Cheeseboard, Lanzarote) and other ancient calendars (Telde, Gran Canaria), cart-ruts and possible pyramids could put Canarian prehistory back much earlier. Origin of these incise linear rock scripts could be found comparing them with European Runes, Iberian, Etruscan and other Old Italian writings (Raetian, Venetian, Lepontic) and also with Sitovo and Gradeshnitsa inscriptions (Bulgaria, dated at least 5,000 years BP). Similar African scripts have also been found in Tunisia. Whether Canarian Iberian-Guanche incise lineal script is origin of any or some of the above mentioned similar scripts or vice versa is open. Finally, population genetics is not a tool to draw absolute conclusions to define origin or population relatedness (i.e.: Canarians) , if it is not used in conjunction with other Anthropology branches , like Archaeology, Language, writing systems, paleoAnatomy and other Culture traits. Keywords : Rock Scripts, Inscriptions, Canary Islands, Iberian, Guanche, Lybic, Lanzarote, Fuerteventura, Quesera, Cheeseboard, Pyramids, Berber, Africa, Punic, Roman, Western Sahara, Tunissia, Sitovo, Gradeshnitsa, Runes, Iberian, Etruscan, Venetian, Lepontic, Raetic, Lybic, The Rock of the Dead, Calendar. Gran Canaria, Tenerife, La Palma, El Hierro, La Gomera, letreros, Roca del Muerto , Basque-Iberian, Vascoiberismo.

“Latín” rock scripts in Canary Islands are ancient Iberian inscriptions (Iberian-Guanche) A story of forgotten genetics, scripts, pyramids and other prehistoric artifacts

“Latin” rock scripts were discovered 30 years ago in Lanzarote and Fuerteventura Islands (Canary Islands). However, they are an incised linear writing which lacks Q, H, P and T frequent Latin letters and translation into Latin has not been possible. A transcription and a translation hypothesis was proposed long ago because scripts were almost identical to those of the Iberian semi-syllabary which was used in Iberia and France during first millennium BC; “Latin” scripts were named “IberianGuanche” and were mostly religious and funerary. This type of lineal incise writing is present in all seven Canary Islands and they may have been unnoticed because all other islands except Lanzarote and Fuerteventura are humid and covered by vegetation. This type of linear writings are, like Iberian, similar to Runes (Atlantic and Central Europe),Old Italian scripts (Raetian, Venetic, Lepontic, Etruscan) and Sitovo and Gradeshnistsa scripts (Bulgaria, 5th millennium BC). Language behind Iberian-Guanche scripts might be related to both Berber and Old Basque languages. People who wrote “Iberian-Guanche” inscriptions seem to be Canary Island inhabitants and not visitors. Genes (people) of present and past Canary Islanders are difficult only to assign to North Africa because gene flow between North Africa and Iberia existed in prehistoric times and it is difficult to distinguish Iberian and North African with Canarian gene profiles. Genetics by itself is not sufficient for relating people or specific for geography, this is firmly demonstrated for mitochondrial genes. Linguistics, Culture, and Archaeology are necessary to interpret population genetics data. Extant pyramids in North Africa, Western Sahara and possibly Tenerife, existence of prehistoric artifacts and rock calendars (“Quesera”/Cheeseborad lunisolar calendar at Lanzarote and others at Gran Canaria Island) and presence of Cart-Ruts on Lanzarote volcano tops, may indicate an older date for Canarian prehistory than that of Punic/Roman presence. Finally Canarian prehistoric findings have been long neglected and forgotten but a common IberianGuanche rock writing culture existed in Canary Islands. Keywords : Latin, Scripts, Canary Islands, Iberian, Guanche, Lybic, Lanzarote, Fuerteventura, Quesera, Cheeseboard, Pyramids, Berber, Africa, Punic, Roman, Western Sahara, Tunisia, Algeria, Canarian, Semi-Sillabary, Calendar, Raetian, Lepontic, Venetian, Etruscan, Basque, Cart-ruts, Sitovo, Gradeshnitsa, UskoMediterranean.

Vascular endothelial growth factor A (VEGF-A) amplification and long-term response to ramucirumab (ram) in metastatic gastric cancer (mGC): The VERA study.

3143 Background: The anti-VEGFR-2 monoclonal antibody ram, alone or with paclitaxel, is a cornerstone of second-line treatment of mGC. Even if about half patients do not benefit from ram, no predictive biomarkers have been identified so far. In TCGA, VEGF-A amplification was found in 7% of cases, almost exclusively in chromosomal instability subtype. We hypothesize that VEGF-A amplification in tumor cells could lead to autocrine/paracrine stimulation of tumor growth beside angiogenesis, potentially identifying a patients’ subgroup with exceptional responses to ram. Methods: VERA was a multicentric, prospective study based on a translational hypothesis. mGC patients were included according to the following criteria: 1) complete (CR) or partial response (PR) to single-agent ram; 2) >6 months PFS to single-agent ram; 3) >10 months PFS to paclitaxel+ram. According to a Fleming single-stage design, hypothesizing a prevalence of VEGF-A amplification of 1% and 15% among all-comers and exceptional responders, 20 exceptional responders were required to reject the null hypothesis of low prevalence of VEGF-A amplification, with alpha- and beta- errors of 0.05 and 0.10, respectively. VEGF-A amplification (defined as >10% tumor cells with ≥10 VEGF-A copies, variably sized signal clusters or a ratio of VEGF-A gene to centromere of ≥2) was centrally assessed through fluorescent in situ hybridization on pre-treatment FFPE tumor tissue. Results: At 7 Italian Centers, we included 20 patients satisfying the 1st (n=1), 2nd (n=2), or 3rd (n=17) criterion. Clinical-pathological features were: M/F, 11/9; median age 63 years; gastric/GEJ, 17/3; intestinal/diffuse, 14/6, HER2+/HER2-, 4/16. Median PFS and overall survival to ram-based treatment were 15.6 and 25.7 months, with best response: CR/PR/SD, 0/10/10. VERA met its primary endpoint, revealing 3/20 (15%) tumors with VEGF-A amplification (1 case presenting big clusters, 1 small clusters and 1 with >10% tumor cells with ≥10 VEGF-A copies). Conclusions: Validation analyses of first- and second-line randomized trials could confirm VEGF-A amplification as a biomarker of long-term response to ram-based treatment in mGC patients, advancing treatment personalization.