Norupconway3896

How we perceive a visual scene depends critically on the selection of gaze positions. For this selection process, visual attention is known to play a key role in two ways. First, image-features attract visual attention, a fact that is captured well by time-independent fixation models. Second, millisecond-level attentional dynamics around the time of saccade drives our gaze from one position to the next. These two related research areas on attention are typically perceived as separate, both theoretically and experimentally. Here we link the two research areas by demonstrating that perisaccadic attentional dynamics improve predictions on scan path statistics. In a mathematical model, we integrated perisaccadic covert attention with dynamic scan path generation. Our model reproduces saccade amplitude distributions, angular statistics, intersaccadic turning angles, and their impact on fixation durations as well as inter-individual differences using Bayesian inference. Therefore, our result lend support to the relevance of perisaccadic attention to gaze statistics.Cold Atmospheric pressure Plasma (CAP) is a non-thermal method used in food processing. CAP generated with the use of nitrogen in a Glide-arc device for 300 to 600 s exhibited high potential for microbial decontamination and did not induce substantial changes in the physicochemical properties of NFC tomato juice. Samples exposed to cold atmospheric plasma had mostly an intact structure, as revealed by digital microscopy. The investigations indicate that CAP can be applied for biological and chemical waste-free decontamination of food and extension of its shelf life.The advent of metal processing was one of the key technological evolutions presaging the development of modern society. However, the interplay between metal use and the long-term changes it induced in the development and functioning of past societies remains unclear. We present a compilation of global records of anthropogenic atmospheric lead (Pb) spanning the last 4000 years, an effective indirect proxy for reliably assessing Pb emissions directly linked to human activities. Separating this global Pb pollution signal into regionally representative clusters allows identification of regional differences in pollution output that reflect technological innovations, market demands, or demise of various human cultures for last 4000 years. Our European reconstruction traces well periods of intensive metal production such as the Roman and Medieval periods, in contrast to clusters from the Americas, which show low levels of atmospheric Pb until the Industrial Revolution. Further investigation of the European synthesis results displays clear regional variation in the timing and extent of past development of polluting activities. This indicates the challenges of using individual reconstructions to infer regional or global development in Pb output and related pollution.Based on a previous study that demonstrated the beneficial effects of sonification on cycling performance, this study investigated which kinematic and muscular activities were changed to pedal effectively. An online error-based sonification strategy was developed, such that, when negative torque was applied to the pedal, a squeak sound was produced in real-time in the corresponding headphone. Participants completed four 6-min cycling trials with resistance values associated with their first ventilatory threshold. Different auditory display conditions were used for each trial (Silent, Right, Left, Stereo), where sonification was only presented for 20 s at the start of minutes 1, 2, 3, and 4. Joint kinematics and right leg muscular activities of 10 muscles were simultaneously recorded. Our results showed participants were more effective at pedalling when presented sonification, which was consistent with previously reported findings. In comparison to the Silent condition, sonification significantly limited ankle and knee joint ranges of motion and reduced muscular activations. These findings suggest performance-based sonification significantly affected participants to reduce the complexity of the task by altering the coordination of the degrees of freedom. By making these significant changes to their patterns, participants improved their cycling performance despite lowering joint ranges of motion and muscular activations.Hypospadias is a common abnormality of the urogenital tract with a wide range of variety in its presentation and severity. The primary aim to correct hypospadias is to restore normal penile function and appearance. Although it can be corrected at any age, early correction between the 6 and 18 months of life is recommended. The functional and cosmetic outcomes have been very-well presented in the literature, although the aspects of sexuality and fertility of hypospadias repair in the long term are vague. In this narrative review, we aimed to gather the data around the sexuality and fertility outcomes of hypospadias repair and acknowledge urologists and parents of boys with hypospadias who will have a correction surgery about future sexual and fertility concerns.POEMS syndrome is a rare plasma cell dyscrasia. Little is known about its pathogenesis and genetic features. click here We analyzed the mutational features of purified bone marrow plasma cells from 42 patients newly diagnosed with POEMS syndrome using a two-step strategy. Whole exome sequencing of ten patients showed a total of 170 somatic mutations in exonic regions and splicing sites, with paired peripheral blood mononuclear cells as a control. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, and CUX1) were identified. Target region sequencing of 77 genes were then analyzed to validate the mutations in an additional 32 patients. A total of 32 mutated genes were identified, and genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, and ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Our study revealed heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome, which might share some similarity to that of other plasma cell diseases.Pharmacological inhibition of MDM2/4, which activates the critical tumor suppressor p53, has been gaining increasing interest as a strategy for the treatment of acute myeloid leukemia (AML). While clinical trials of MDM2 inhibitors have shown promise, responses have been confined to largely molecularly undefined patients, indicating that new biomarkers and optimized treatment strategies are needed. We previously reported that the microRNA miR-10a is strongly overexpressed in some AML, and demonstrate here that it modulates several key members of the p53/Rb network, including p53 regulator MDM4, Rb regulator RB1CC1, p21 regulator TFAP2C, and p53 itself. The expression of both miR-10a and its downstream targets were strongly predictive of MDM2 inhibitor sensitivity in cell lines, primary AML specimens, and correlated to response in patients treated with both MDM2 inhibitors and cytarabine. Furthermore, miR-10a inhibition induced synergy between MDM2 inhibitor Nutlin-3a and cytarabine in both in vitro and in vivo AML models. Mechanistically this synergism primarily occurs via the p53-mediated activation of cytotoxic apoptosis at the expense of cytoprotective autophagy. Together these findings demonstrate that miR-10a may be useful as both a biomarker to identify patients most likely to respond to cytarabine+MDM2 inhibition and also a druggable target to increase their efficacy.Structural chromosomal changes including copy number aberrations (CNAs) are a major feature of multiple myeloma (MM), however their evolution in context of modern biological therapy is not well characterized. To investigate acquisition of CNAs and their prognostic relevance in context of first-line therapy, we profiled tumor diagnosis-relapse pairs from 178 NCRI Myeloma XI (ISRCTN49407852) trial patients using digital multiplex ligation-dependent probe amplification. CNA profiles acquired at relapse differed substantially between MM subtypes hyperdiploid (HRD) tumors evolved predominantly in branching pattern vs. linear pattern in t(4;14) vs. stable pattern in t(11;14). CNA acquisition also differed between subtypes based on CCND expression, with a marked enrichment of acquired del(17p) in CCND2 over CCND1 tumors. Acquired CNAs were not influenced by high-dose melphalan or lenalidomide maintenance randomization. A branching evolution pattern was significantly associated with inferior overall survival (OS; hazard ratio (HR) 2.61, P = 0.0048). As an individual lesion, acquisition of gain(1q) at relapse was associated with shorter OS, independent of other risk markers or time of relapse (HR = 2.00; P = 0.021). There is an increasing need for rational therapy sequencing in MM. Our data supports the value of repeat molecular profiling to characterize disease evolution and inform management of MM relapse.An amendment to this paper has been published and can be accessed via a link at the top of the paper.A potentially important aspect in the regulation of tumour metastasis is endocytosis. This process consists of internalisation of cell-surface receptors via pinocytosis, phagocytosis or receptor-mediated endocytosis, the latter of which includes clathrin-, caveolae- and non-clathrin or caveolae-mediated mechanisms. Endocytosis then progresses through several intracellular compartments for sorting and routing of cargo, ending in lysosomal degradation, recycling back to the cell surface or secretion. Multiple endocytic proteins are dysregulated in cancer and regulate tumour metastasis, particularly migration and invasion. Importantly, four metastasis suppressor genes function in part by regulating endocytosis, namely, the NME, KAI, MTSS1 and KISS1 pathways. Data on metastasis suppressors identify a new point of dysregulation operative in tumour metastasis, alterations in signalling through endocytosis. This review will focus on the multicomponent process of endocytosis affecting different steps of metastasis and how metastatic-suppressor genes use endocytosis to suppress metastasis.Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours.