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High-harmonic generation (HHG) in solids is a powerful and versatile method for ultrafast spectroscopy, as shown in resent studies, including all-optical band reconstructions [1] , exciton analysis [2] and valence electron mapping [3] . Additionally, solid-state targets offer the possibility for an intrinsic control of HHG by integrated optoelectronics [4] or by tailoring the polarization of the driving field to the crystal symmetry. In gases, the light-matter symmetry is governed by the laser alone, as demonstrated in the generation of circularly polarized high harmonics from tailored bi-circular fields [5] . In solids, on the other hand, emitted high-order harmonics would have an interplay with the crystalline structure, thus open new avenues for symmetry-sensitive spectroscopy., 2021 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC), June 21-25, 2021, Munich, Germany

Recent work has shown that linguistic and visual contexts jointly modulate linguistic expectancy and, thus, the processing effort for a (more or less) expected critical word (Ankener et al., 2018; Tourtouri et al., 2019; Staudte et al., 2020). According to these findings, uncertainty about the upcoming referent in a visually-situated sentence can be reduced by exploiting the selectional restrictions of a preceding word (e.g., a verb or an adjective), which then reduces processing effort on the critical word (e.g., a referential noun). Interestingly, however, no such modulation was observed in these studies on the expectation-generating word itself. The goal of the current study is to investigate whether the reduction of uncertainty (i.e., the generation of expectations) simply does not modulate processing effort --- or whether the particular subject-verb-object (SVO) sentence structure used in these studies (which emphasizes the referential nature of the noun as direct pointer to visually co-present objects) accounts for the observed pattern. To test these questions, the current design reverses the functional roles of nouns and verbs by using sentence constructions in which the noun reduces uncertainty about upcoming verbs, and the verb provides the disambiguating and reference-resolving piece of information. Experiment~1 (a Visual World Paradigm study) and Experiment~2 (a Grammaticality Maze study) both replicate the effect found in Ankener et al. (2018) of visually-situated context on the word which uniquely identifies the referent, albeit on the verb in the current study. Results on the noun, where uncertainty is reduced and expectations are generated in the current design, were mixed and were most likely influenced by design decisions specific to each experiment. These results show that processing of the reference-resolving word --- whether it be a noun or a verb --- reliably benefits from the prior linguistic and visual information that lead to the generation of concrete expectations.

Measuring the field of visible light with high spatial resolution has been challenging, as many established methods only detect a focus-averaged signal. Here, we introduce a near-field method for optical field sampling that overcomes that limitation by employing the localization of the enhanced near-field of a nanometric needle tip. A probe field perturbs the photoemission from the tip, which is induced by a pump pulse, generating a field-dependent current modulation that can easily be captured with our electronic detection scheme. The approach provides reliable characterization of near-petahertz fields. We show that not only the spiral wavefront of visible femtosecond light pulses carrying orbital angular momentum (OAM) can be resolved but also the field evolution with time in the focal plane. Additionally, our method is polarization sensitive, which makes it applicable to vectorial field reconstruction.

SUMMARYRecent data suggests that colon tumors contain a subpopulation of therapy resistant quiescent cancer stem cells (qCSCs) that are the source of relapse following treatment. Here, using colon cancer patient-derived organoids (PDOs) and xenograft (PDX) models, we identify a rare population of long-term label-retaining (PKH26Positive) qCSCs that can re-enter the cell cycle to generate new tumors. RNA-sequencing analyses demonstrated that these cells are enriched for stem cell associated gene sets such as Wnt and hedgehog signaling, epithelial-to-mesenchymal transition (EMT), embryonic development, tissue development and p53 pathway but have downregulated expression of genes associated with cell cycle, transcription, biosynthesis and metabolism. Furthermore, qCSCs are enriched for p53 interacting negative regulators of cell cycle, includingAKAP12, CD82, CDKN1A, FHL2, GPX3, KIAA0247, LCN2, TFF2, UNC5BandZMAT3, that we show are indicators of poor prognosis and may be targeted for qCSC abolition. Interestingly, CD82, KIAA0247 and UNC5B proteins localize to the cell surface and may therefore be potential markers for the prospective isolation of qCSCs. These data support the temporal inhibition of p53 signaling for the elimination of qCSCs and prevention of relapse in colorectal cancer.

SUMMARYRecent data support a hierarchical model of colon cancer driven by a population of cancer stem cells (CSCs). Greater understanding of the mechanisms that regulate CSCs may therefore lead to more effective treatments. Serial limiting dilution xenotransplantation assays of colon cancer patient-derived tumors demonstrated ALDHPositivecells to be enriched for tumorigenic self-renewing CSCs. In order to identify CSC modulators, we performed RNA-sequencing analysis of ALDHPositiveCSCs from a panel of colon cancer patient-derived organoids (PDOs) and xenografts (PDXs). These studies demonstrated CSCs to be enriched for embryonic and neural development gene sets. Functional analyses of genes differentially expressed in both ALDHPositivePDO and PDX CSCs demonstrated the neural crest stem cell (NCSC) regulator and wound response geneEGR2to be required for CSC tumorigenicity and to control expression of homeobox superfamily embryonic master transcriptional regulatorHOXgenes and the embryonic and neural stem cell regulatorSOX2. In addition, we identifyEGR2,HOXA2,HOXA4,HOXA5,HOXA7,HOXB2,HOXB3and the tumor suppressorATOH1as new prognostic biomarkers in colorectal cancer.

We present a novel approach to single-shot characterization of the spectral phase of broadband laser pulses. Our method is inexpensive, insensitive to alignment and combines the simplicity and robustness of the dispersion scan technique, that does not require spatio-temporal pulse overlap, with the advantages of single-shot pulse characterization methods such as single-shot frequency-resolved optical gating at a real-time reconstruction rate of several Hz.

The quantile ratio index is a simple and effective measure of relative inequality for income data that is resistant to outliers. A useful property of this index is investigated here: Given a partition of the income distribution into a union of sets of symmetric quantiles, one can find the inequality for each set and readily combine them in a weighted average to obtain the index for the entire population. When applied to data for various years, one can track how these contributions to inequality vary over time, as illustrated here for Australian Bureau of Statistics income and wealth data.

Chi-squared tests for lack of fit are traditionally employed to find evidence against a hypothesized model, with the model accepted if the Karl Pearson statistic comparing observed and expected numbers of observations falling within cells is not significantly large. However, if one really wants evidence for goodness of fit, it is better to adopt an equivalence testing approach in which small values of the chi-squared statistic indicate evidence for the desired model. This method requires one to define what is meant by equivalence to the desired model, and guidelines are proposed. It is shown that the evidence for equivalence can distinguish between normal and nearby models, as well between the Poisson and over-dispersed models. Applications to the evaluation of random number generators and to uniformity of the digits of pi are included. Sample sizes required to obtain a desired expected evidence for goodness of fit are also provided.

Summary Recent data suggest that therapy-resistant quiescent cancer stem cells (qCSCs) are the source of relapse in colon cancer. Here, using colon cancer patient-derived organoids and xenografts, we identify rare long-term label-retaining qCSCs that can re-enter the cell cycle to generate new tumors. RNA sequencing analyses demonstrated that these cells display the molecular hallmarks of quiescent tissue stem cells, including expression of p53 signaling genes, and are enriched for transcripts common to damage-induced quiescent revival stem cells of the regenerating intestine. In addition, we identify negative regulators of cell cycle, downstream of p53, that we show are indicators of poor prognosis and may be targeted for qCSC abolition in both p53 wild-type and mutant tumors. These data support the temporal inhibition of downstream targets of p53 signaling, in combination with standard-of-care treatments, for the elimination of qCSCs and prevention of relapse in colon cancer., Graphical Abstract, Highlights • Colon tumors contain therapy-resistant quiescent cancer stem cells (qCSCs) • qCSC gene expression mirrors that of quiescent stem cells of the regenerating gut • qCSCs are enriched for p53 signaling genes • qCSC elimination may be achieved by inhibiting downstream targets of p53 signaling, Cancer stem cells ; Quiescence; Organoids; Colon cancer; p53 signaling; Transcriptomics

Recent evidence demonstrates that colon cancer stem cells (CSCs) can generate neurons that synapse with tumor innervating fibers required for tumorigenesis and disease progression. Greater understanding of the mechanisms that regulate CSC driven tumor neurogenesis may therefore lead to more effective treatments. RNA-sequencing analyses of ALDH

We demonstrate a novel method to measure the temporal electric field evolution of ultrashort laser pulses. Our technique is based on the detection of transient currents in air plasma. These directional currents result from subcycle ionization of air with a short pump pulse and the steering of the released electrons with the pulse to be sampled. We assess the validity of our approach by comparing it with different state-of-the-art laser-pulse characterization techniques. Notably, our method works in ambient air and facilitates a direct measurement of the field waveform, which can be viewed in real time on an oscilloscope in a similar way as a radio frequency signal.

Strong-field methods in solids enable new strategies for ultrafast nonlinear spectroscopy and provide all-optical insights into the electronic properties of condensed matter in reciprocal and real space. Additionally, solid-state media offers unprecedented possibilities to control high-harmonic generation using modified targets or tailored excitation fields. Here we merge these important points and demonstrate circularly-polarized high-harmonic generation with polarization-matched excitation fields for spectroscopy of chiral electronic properties at surfaces. The sensitivity of our approach is demonstrated for structural helicity and termination-mediated ferromagnetic order at the surface of silicon-dioxide and magnesium oxide, respectively. Circularly polarized radiation emanating from a solid sample now allows to add basic symmetry properties as chirality to the arsenal of strong-field spectroscopy in solids. Together with its inherent temporal (femtosecond) resolution and non-resonant broadband spectrum, the polarization control of high harmonics from condensed matter can illuminate ultrafast and strong field dynamics of surfaces, buried layers or thin films., 24 pages, 5 figures

Detection of circulating tumor cells (CTCs) has been established as an independent prognostic marker in solid cancer. Multiparametric phenotyping of CTCs could expand the area of application for this liquid biomarker. We evaluated the Amnis® brand ImageStream®X MkII (ISX) (Luminex, Austin, TX, USA) imaging flow cytometer for its suitability for protein expression analysis and monitoring of treatment effects in CTCs. This was carried out using blood samples from patients with head and neck squamous cell carcinoma (n = 16) and breast cancer (n = 8). A protocol for negative enrichment and staining of CTCs was established, allowing quantitative analysis of the therapeutic targets PD–L1 and phosphorylated EGFR (phospho–EGFR), and the treatment response marker γH2AX as an indicator of radiation–induced DNA damage. Spiking experiments revealed a sensitivity of 73% and a specificity of 100% at a cut–off value of ≥3 CTCs, and thus confirmed the suitability of the ISX-based protocol to detect phospho–EGFR and γH2AX foci in CTCs. Analysis of PD–L1/–L2 in both spiked and patient blood samples further showed that assessment of heterogeneity in protein expression within the CTC population was possible. Further validation of the diagnostic potential of this ISX protocol for multiparametric CTC analysis in larger clinical cohorts is warranted.

Referential gaze has been shown to benefit language processing in situated communication in terms of shifting visual attention and leading to shorter reaction times on subsequent tasks. The present study simultaneously assessed both visual attention and, importantly, the immediate cognitive load induced at different stages of sentence processing. We aimed to examine the dynamics of combining visual and linguistic information in creating anticipation for a specific object and the effect this has on language processing. We report evidence from three visual‐world eye‐tracking experiments, showing that referential gaze leads to a shift in visual attention toward the cued object, which consequently lowers the effort required for processing the linguistic reference. Importantly, perceiving and following the gaze cue did not prove costly in terms of cognitive effort, unless the cued object did not fit the verb selectional preferences.