CIL 6.1300 – Fragment of a dedication (perhaps a copy?) from the base of a ‘columna rostrata’ honoring Gaius Duilius, hero of the First Punic War

Photographs

Maternal Copy Number Variants (CNV) transmission to their Autism Spectrum Disorder (ASD) sons correlates with phenotypic traits

Background: Common neurodevelopmental disorder, global prevalence ~1 %; Persistent deficits in social communication and social interaction; restricted and repetitive behavior, interests, or activities; Highly heterogeneous clinical presentation; Male to female ratio ~4:1.

Copy from actual survey of the 3 Sisters : [Potomac River, Washington D.C.] /

Cadastral map.

Syriac–Aramaic words in an early Christian Arabic copy of the Pentateuch (Ms Sin. Ar. 2)

Este artículo se ocupa de las voces siriaco arameas incluidas en las primeras copias del Pentateuco (ms. Sin. ar. 2) del siglo X, que fueron traducidas a partir de la Peshīṭtā. Uno de sus reasgos más característicos es la existencia de residuos siriaco-arameos, especialmente en las palabras siriaco-arameas que no son comunes al árabe.

Genome-wide copy number variation (CNV) detection in Nelore cattle reveals highly frequent variants in genome regions harboring QTLs affecting production traits.

Background: Copy number variations (CNVs) have been shown to account for substantial portions of observed genomic variation and have been associated with qualitative and quantitative traits and the onset of disease in a number of species. Information from high-resolution studies to detect, characterize and estimate population-specific variant frequencies will facilitate the incorporation of CNVs in genomic studies to identify genes affecting traits of importance. Results: Genome-wide CNVs were detected in high-density single nucleotide polymorphism (SNP) genotyping data from 1,717 Nelore (Bos indicus) cattle, and in NGS data from eight key ancestral bulls. A total of 68,007 and 12,786 distinct CNVs were observed, respectively. Cross-comparisons of results obtained for the eight resequenced animals revealed that 92 % of the CNVs were observed in both datasets, while 62 % of all detected CNVs were observed to overlap with previously validated cattle copy number variant regions (CNVRs). Observed CNVs were used for obtaining breed-specific CNV frequencies and identification of CNVRs, which were subsequently used for gene annotation. A total of 688 of the detected CNVRs were observed to overlap with 286 non-redundant QTLs associated with important production traits in cattle. All of 34 CNVs previously reported to be associated with milk production traits in Holsteins were also observed in Nelore cattle. Comparisons of estimated frequencies of these CNVs in the two breeds revealed 14, 13, 6 and 14 regions in high (>20 %), low (<20 %) and divergent (NEL > HOL, NEL < HOL) frequencies, respectively. Conclusions: Obtained results significantly enriched the bovine CNV map and enabled the identification of variants that are potentially associated with traits under selection in Nelore cattle, particularly in genome regions harboring QTLs affecting production traits.

Small-plasmid-mediated antibiotic resistance is enhanced by increases in plasmid copy number and bacterial fitness

Plasmids play a key role in the horizontal spread of antibiotic resistance determinants among bacterial pathogens. When an antibiotic resistance plasmid arrives in a new bacterial host, it produces a fitness cost, causing a competitive disadvantage for the plasmid-bearing bacterium in the absence of antibiotics. On the other hand, in the presence of antibiotics, the plasmid promotes the survival of the clone. The adaptations experienced by plasmid and bacterium in the presence of antibiotics during the first generations of coexistence will be crucial for the progress of the infection and the maintenance of plasmid-mediated resistance once the treatment is over. Here we developed a model system using the human pathogen Haemophilus influenzae carrying the small plasmid pB1000 conferring resistance to β-lactam antibiotics to investigate host and plasmid adaptations in the course of a simulated ampicillin therapy. Our results proved that plasmid-bearing clones compensated for the fitness disadvantage during the first 100 generations of plasmid-host adaptation. In addition, ampicillin treatment was associated with an increase in pB1000 copy number. The augmentation in both bacterial fitness and plasmid copy number gave rise to H. influenzae populations with higher ampicillin resistance levels. In conclusion, we show here that the modulations in bacterial fitness and plasmid copy number help a plasmid-bearing bacterium to adapt during antibiotic therapy, promoting both the survival of the host and the spread of the plasmid.

‘‘Model age-based” and ‘‘copy when uncertain” biases in children’s social learning of a novel task

Theoretical models of social learning predict that individuals can benefit from using strategies that specify when and whom to copy. Here the interaction of two social learning strategies, model age-based biased copying and copy when uncertain, was investigated. Uncertainty was created via a systematic manipulation of demonstration efficacy (completeness) and efficiency (causal relevance of some actions). The participants, 4- to 6-year-old children (N = 140), viewed both an adult model and a child model, each of whom used a different tool on a novel task. They did so in a complete condition, a near-complete condition, a partial demonstration condition, or a no-demonstration condition. Half of the demonstrations in each condition incorporated causally irrelevant actions by the models. Social transmission was assessed by first responses but also through children’s continued fidelity, the hallmark of social traditions. Results revealed a bias to copy the child model both on first response and in continued interactions. Demonstration efficacy and efficiency did not affect choice of model at first response but did influence solution exploration across trials, with demonstrations containing causally irrelevant actions decreasing exploration of alternative methods. These results imply that uncertain environments can result in canalized social learning from specific classes of mode

Do children copy an expert or a majority? Examining selective learning in instrumental and normative contexts

This study examined whether instrumental and normative learning contexts differentially influence 4- to 7-year-old children’s social learning strategies; specifically, their dispositions to copy an expert versus a majority consensus. Experiment 1 (N = 44) established that children copied a relatively competent “expert” individual over an incompetent individual in both kinds of learning context. In experiment 2 (N = 80) we then tested whether children would copy a competent individual versus a majority, in each of the two different learning contexts. Results showed that individual children differed in strategy, preferring with significant consistency across two different test trials to copy either the competent individual or the majority. This study is the first to show that children prefer to copy more competent individuals when shown competing methods of achieving an instrumental goal (Experiment 1) and provides new evidence that children, at least in our “individualist” culture, may consistently express either a competency or majority bias in learning both instrumental and normative information (Experiment 2). This effect was similar in the instrumental and normative learning contexts we applied.

TiMMing: developing an innovative suite of bioinformatic tools to harmonize and track the origin of copy number alterations in the evolutive history of multiple myeloma

Multiple Myeloma (MM) is a hematologic cancer with heterogeneous and complex genomic landscape, where Copy Number Alterations (CNAs) play a key role in the disease's pathogenesis and prognosis. It is of biological and clinical interest to study the temporal occurrence of early alterations, as they play a disease "driver" function by deregulating key tumor pathways. This study presents an innovative bioinformatic tools suite created for harmonizing and tracing the origin of CNAs throughout the evolutionary history of MM. To this aim, large cohorts of newly-diagnosed MM (NDMM, N=1582) and Smoldering-MM (SMM, N=282) were aggregated. The tools developed in this study enable the harmonization of CNAs as obtained from different genomic platforms in such a way that a high statistical power can be obtained. By doing so, the high numerosity of those cohorts was harnessed for the identification of novel genes characterized as "driver" (NFKB2, NOTCH2, MAX, EVI5 and MYC-ME2-enhancer), and the generation of an innovative timing model, implemented with a statistical method to introduce confidence intervals in the CNAs-calls. By applying this model on both NDMM and SMM cohorts, it was possible to identify specific CNAs (1q(CKS1B)amp, 13q(RB1)del, 11q(CCND1)amp and 14q(MAX)del) and categorize them as "early"/ "driver" events. A high level of precision was guaranteed by the narrow confidence intervals in the timing estimates. These CNAs were proposed as critical MM alterations, which play a foundational role in the evolutionary history of both SMM and NDMM. Finally, a multivariate survival model was able to identify the independent genomic alterations with the greatest effect on patients’ survival, including RB1-del, CKS1B-amp, MYC-amp, NOTCH2-amp and TRAF3-del/mut. In conclusion, the alterations that were identified as both "early-drivers” and correlated with patients’ survival were proposed as biomarkers that, if included in wider survival models, could provide a better disease stratification and an improved prognosis definition.

Black hole scattering from Worldline Quantum Field Theory and the Classical Double Copy of Spinning particles

This PhD thesis focuses on studying the classical scattering of massive/massless particles toward black holes, and investigating double copy relations between classical observables in gauge theories and gravity. This is done in the Post-Minkowskian approximation i.e. a perturbative expansion of observables controlled by the gravitational coupling constant κ = 32πGN, with GN being the Newtonian coupling constant. The investigation is performed by using the Worldline Quantum Field Theory (WQFT), displaying a worldline path integral describing the scattering objects and a QFT path integral in the Born approximation, describing the intermediate bosons exchanged in the scattering event by the massive/massless particles. We introduce the WQFT, by deriving a relation between the Kosower- Maybee-O’Connell (KMOC) limit of amplitudes and worldline path integrals, then, we use that to study the classical Compton amplitude and higher point amplitudes. We also present a nice application of our formulation to the case of Hard Thermal Loops (HTL), by explicitly evaluating hard thermal currents in gauge theory and gravity. Next we move to the investigation of the classical double copy (CDC), which is a powerful tool to generate integrands for classical observables related to the binary inspiralling problem in General Relativity. In order to use a Bern-Carrasco-Johansson (BCJ) like prescription, straight at the classical level, one has to identify a double copy (DC) kernel, encoding the locality structure of the classical amplitude. Such kernel is evaluated by using a theory where scalar particles interacts through bi-adjoint scalars. We show here how to push forward the classical double copy so to account for spinning particles, in the framework of the WQFT. Here the quantization procedure on the worldline allows us to fully reconstruct the quantum theory on the gravitational side. Next we investigate how to describe the scattering of massless particles off black holes in the WQFT.

Identification of outcome-oriented cut-offs for copy number alterations in multiple myeloma: predictive biomarkers with improved prognostic accuracy

Aim of the present study was to develop a statistical approach to define the best cut-off Copy number alterations (CNAs) calling from genomic data provided by high throughput experiments, able to predict a specific clinical end-point (early relapse, 18 months) in the context of Multiple Myeloma (MM). 743 newly diagnosed MM patients with SNPs array-derived genomic and clinical data were included in the study. CNAs were called both by a conventional (classic, CL) and an outcome-oriented (OO) method, and Progression Free Survival (PFS) hazard ratios of CNAs called by the two approaches were compared. The OO approach successfully identified patients at higher risk of relapse and the univariate survival analysis showed stronger prognostic effects for OO-defined high-risk alterations, as compared to that defined by CL approach, statistically significant for 12 CNAs. Overall, 155/743 patients relapsed within 18 months from the therapy start. A small number of OO-defined CNAs were significantly recurrent in early-relapsed patients (ER-CNAs) - amp1q, amp2p, del2p, del12p, del17p, del19p -. Two groups of patients were identified either carrying or not ≥1 ER-CNAs (249 vs. 494, respectively), the first one with significantly shorter PFS and overall survivals (OS) (PFS HR 2.15, p<0001; OS HR 2.37, p<0.0001). The risk of relapse defined by the presence of ≥1 ER-CNAs was independent from those conferred both by R-IIS 3 (HR=1.51; p=0.01) and by low quality (< stable disease) clinical response (HR=2.59 p=0.004). Notably, the type of induction therapy was not descriptive, suggesting that ER is strongly related to patients’ baseline genomic architecture. In conclusion, the OO- approach employed allowed to define CNAs-specific dynamic clonality cut-offs, improving the CNAs calls’ accuracy to identify MM patients with the highest probability to ER. As being outcome-dependent, the OO-approach is dynamic and might be adjusted according to the selected outcome variable of interest.

Copy-paste data augmentation for domain transfer on traffic signs

City streets carry a lot of information that can be exploited to improve the quality of the services the citizens receive. For example, autonomous vehicles need to act accordingly to all the element that are nearby the vehicle itself, like pedestrians, traffic signs and other vehicles. It is also possible to use such information for smart city applications, for example to predict and analyze the traffic or pedestrian flows. Among all the objects that it is possible to find in a street, traffic signs are very important because of the information they carry. This information can in fact be exploited both for autonomous driving and for smart city applications. Deep learning and, more generally, machine learning models however need huge quantities to learn. Even though modern models are very good at gener- alizing, the more samples the model has, the better it can generalize between different samples. Creating these datasets organically, namely with real pictures, is a very tedious task because of the wide variety of signs available in the whole world and especially because of all the possible light, orientation conditions and con- ditions in general in which they can appear. In addition to that, it may not be easy to collect enough samples for all the possible traffic signs available, cause some of them may be very rare to find. Instead of collecting pictures manually, it is possible to exploit data aug- mentation techniques to create synthetic datasets containing the signs that are needed. Creating this data synthetically allows to control the distribution and the conditions of the signs in the datasets, improving the quality and quantity of training data that is going to be used. This thesis work is about using copy-paste data augmentation to create synthetic data for the traffic sign recognition task.

Down-regulation Of Slc8a1 As A Putative Apoptosis-evasion Mechanism By Modulation Of Calcium Levels In Penile Carcinoma.

The SLC8A1 gene, which encodes the Na(+)/Ca(2+) exchanger, plays a key role in calcium homeostasis. Our previous gene expression oligoarray data revealed SLC8A1 underexpression in penile carcinoma (PeCa). The aim of this study was to investigate whether the dysregulation of SLC8A1 expression is associated with apoptosis and cell proliferation in PeCa, via modulation of calcium concentration. The underlying mechanisms of SLC8A1 underexpression were also explored, focusing on copy number alteration and microRNA. Transcript levels of SLC8A1 gene and miR-223 were evaluated by quantitative PCR, comparing PeCa samples with normal glans tissues. SLC8A1 copy number was evaluated by microarray-based comparative genomic hybridization (array-CGH). Caspase-3 and Ki-67 immunostaining, as well as calcium distribution by Laser Ablation Imaging Inductively Coupled Plasma Mass Spectrometry [LA(i)-ICP-MS], were investigated in both normal and tumor samples. Confirming our previous data, SLC8A1 underexpression was detected in PeCa samples (P=0.001) and was not associated with gene copy number loss. In contrast, overexpression of miR-223 (P=0.002) was inversely correlated with SLC8A1 (P=0.015, r=-0.426), its putative repressor. In addition, SLC8A1 underexpression was associated with decreased calcium distribution, high Ki-67 and low caspase-3 immunoexpression in PeCa when compared with normal tissues. Down-regulation of the SLC8A1 gene, most likely mediated by its regulator miR-223, can lead to reduced calcium levels in PeCa and, consequently, to suppression of apoptosis and increased tumor cell proliferation. These data suggest that the miR-223-NCX1-calcium-signaling axis may represent a potential therapeutic approach in PeCa.

Distal 22q11.2 Microduplication Combined With Typical 22q11.2 Proximal Deletion: A Case Report.

The 22q11 chromosomal region contains low copy repeats (LCRs) sequences that mediate non-allelic homologous recombination, which predisposes to copy number variations (CNVs) at this locus. Hemizygous deletions of the proximal 22q11.2 region result in the 22q11.2 deletion syndrome (22q11.2 DS). In addition, 22q11.2 duplications involving the distal LCR22s have been reported. This article describes a patient presenting a 2.5-Mb de novo deletion at proximal 22q11.21 region (between LCRs A-D), combined with a 1.3-Mb maternally inherited duplication at distal 22q11.23 region (between LCRs F-H). The presence of concomitant chromosomal imbalances found in this patient has not been reported previously. Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 deletion syndrome and highlights the difficulty to make genetic counseling and predict phenotypic consequences in these situations.

Resposta eletromiografica do musculo iliocostal lombar e abordagem da pressão intradiscal da coluna lombar

Universidade Estadual de Campinas. Faculdade de Educação Física