Here we provide a unified theoretical description of two different physical situations in which liquid jets are expelled out of the bulk of a liquid as a consequence of the capillary collapse of a ...void. We demonstrate that the velocity field giving rise to the emergence of these jets can be calculated as the flow generated by a line of sinks with a length and an intensity that can be expressed in terms of the initial cavity radius and the wavelength and velocity of the capillary waves propagating along the cavity walls. The predicted jet speeds, which are expressed through algebraic equations, are in good quantitative agreement with those obtained from experiments and from the simulations of bubbles bursting on a free surface or after the implosion of the crater formed when a drop impacts a liquid pool.
Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for ...improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.
This work presents results in the field of advanced substrate solutions in order to achieve high crystalline quality group-III nitrides based heterostructures for high frequency and power devices or ...for sensor applications. With that objective, Low Temperature Co-fired Ceramics has been used, as a non-crystalline substrate. Structures like these have never been developed before, and for economic reasons will represent a groundbreaking material in these fields of Electronic. In this sense, the report presents the characterization through various techniques of three series of specimens where GaN was deposited on this ceramic composite, using different buffer layers, and a singular metal-organic chemical vapor deposition related technique for low temperature deposition. Other single crystalline ceramic-based templates were also utilized as substrate materials, for comparison purposes.
A dense forest of slender bright fibrils near a small solar active region is seen in high-quality narrowband Ca ii H images from the SuFI instrument onboard the Sunrise balloon-borne solar ...observatory. The orientation of these slender Ca ii H fibrils (SCF) overlaps with the magnetic field configuration in the low solar chromosphere derived by magnetostatic extrapolation of the photospheric field observed with Sunrise/IMaX and SDO/HMI. In addition, many observed SCFs are qualitatively aligned with small-scale loops computed from a novel inversion approach based on best-fit numerical MHD simulation. Such loops are organized in canopy-like arches over quiet areas that differ in height depending on the field strength near their roots.
The use of next-generation sequencing technologies has enabled the rapid identification of non-synonymous somatic mutations in cancer cells. Neoantigens are mutated peptides derived from somatic ...mutations not present in normal tissues that may result in the presentation of tumour-specific peptides capable of eliciting antitumour T-cell responses. Personalised neoantigen-based cancer vaccines and adoptive T-cell therapies have been shown to prime host immunity against tumour cells and are under clinical trial development. However, the optimisation and standardisation of neoantigen identification, as well as its delivery as immunotherapy are needed to increase tumour-specific T-cell responses and, thus, the clinical efficacy of current cancer immunotherapies.
In this recommendation article, launched by the European Society for Medical Oncology (ESMO), we outline and discuss the available framework for neoantigen prediction and present a systematic review of the current scientific evidence.
A number of computational pipelines for neoantigen prediction are available. Most of them provide peptide major histocompatibility complex (MHC) binding affinity predictions, but more recent approaches incorporate additional features like variant allele fraction, gene expression, and clonality of mutations. Neoantigens can be predicted in all cancer types with high and low tumour mutation burden, in part by exploiting tumour-specific aberrations derived from mutational frameshifts, splice variants, gene fusions, endogenous retroelements and other tumour-specific processes that could yield more potently immunogenic tumour neoantigens. Ongoing clinical trials will highlight those cancer types and combinations of immune therapies that would derive the most benefit from neoantigen-based immunotherapies.
Improved identification, selection and prioritisation of tumour-specific neoantigens are needed to increase the scope of benefit from cancer vaccines and adoptive T-cell therapies. Novel pipelines are being developed to resolve the challenges posed by high-throughput sequencing and to predict immunogenic neoantigens.
•Next-generation sequencing technologies have provided the means to directly identify somatic gene mutations in tumours.•Neoantigens are tumour-specific mutated peptides capable of inducing antitumour immune responses.•The discovery of immunogenic neoantigens is instrumental for the pursuit of cancer vaccines and adoptive T-cell therapy.•Refining computational workflows towards the optimal identification of immunogenic neoepitopes is needed.
In soft fruits, the differential expression of many genes during development and ripening is responsible for changing their organoleptic properties. In strawberry fruit, although some genes involved ...in the metabolic regulation of the ripening process have been functionally characterized, some of the most studied genes correspond to transcription factors. High throughput transcriptomics analyses performed in strawberry red receptacle (Fragaria x ananassa) allowed us to identify a ripening-related gene that codes an atypical HLH (FaPRE1) with high sequence homology with the PACLOBUTRAZOL RESISTANCE (PRE) genes. PRE genes are atypical bHLH proteins characterized by the lack of a DNA-binding domain and whose function has been linked to the regulation of cell elongation processes.
FaPRE1 sequence analysis indicates that this gene belongs to the subfamily of atypical bHLHs that also includes ILI-1 from rice, SlPRE2 from tomato and AtPRE1 from Arabidopsis, which are involved in transcriptional regulatory processes as repressors, through the blockage by heterodimerization of bHLH transcription factors. FaPRE1 presented a transcriptional model characteristic of a ripening-related gene with receptacle-specific expression, being repressed by auxins and activated by abscisic acid (ABA). However, its expression was not affected by gibberellic acid (GA
). On the other hand, the transitory silencing of FaPRE1 transcription by agroinfiltration in receptacle produced the down-regulation of a group of genes related to the ripening process while inducing the transcription of genes involved in receptacle growth and development.
In summary, this work presents for the first time experimental data that support an important novel function for the atypical HLH FaPRE1 during the strawberry fruit ripening. We hypothesize that FaPRE1 modulates antagonistically the transcription of genes related to both receptacle growth and ripening. Thus, FaPRE1 would repress the expression of receptacle growth promoting genes in the ripened receptacle, while it would activate the expression of those genes related to the receptacle ripening process.
Proteasome inhibitors (PIs), namely bortezomib, have become a cornerstone therapy for multiple myeloma (MM), potently reducing tumor burden and inhibiting pathologic bone destruction. In clinical ...trials, carfilzomib, a next generation epoxyketone-based irreversible PI, has exhibited potent anti-myeloma efficacy and decreased side effects compared with bortezomib. Carfilzomib and its orally bioavailable analog oprozomib, effectively decreased MM cell viability following continual or transient treatment mimicking in vivo pharmacokinetics. Interactions between myeloma cells and the bone marrow (BM) microenvironment augment the number and activity of bone-resorbing osteoclasts (OCs) while inhibiting bone-forming osteoblasts (OBs), resulting in increased tumor growth and osteolytic lesions. At clinically relevant concentrations, carfilzomib and oprozomib directly inhibited OC formation and bone resorption in vitro, while enhancing osteogenic differentiation and matrix mineralization. Accordingly, carfilzomib and oprozomib increased trabecular bone volume, decreased bone resorption and enhanced bone formation in non-tumor bearing mice. Finally, in mouse models of disseminated MM, the epoxyketone-based PIs decreased murine 5TGM1 and human RPMI-8226 tumor burden and prevented bone loss. These data demonstrate that, in addition to anti-myeloma properties, carfilzomib and oprozomib effectively shift the bone microenvironment from a catabolic to an anabolic state and, similar to bortezomib, may decrease skeletal complications of MM.
Cross-coupling reactions have played a critical role enabling the rapid expansion of structure-activity relationships (SAR) during the drug discovery phase to identify a clinical candidate and ...facilitate subsequent drug development processes. The reliability and flexibility of this methodology have attracted great interest in the pharmaceutical industry, becoming one of the most used approaches from Lead Generation to Lead Optimization. In this mini-review, we present an overview of cross-coupling reaction applications to medicinal chemistry efforts, in particular the Suzuki-Miyaura and Buchwald-Hartwig cross-coupling reactions as a remarkable resource for the generation of carbon-carbon and carbon-heteroatom bonds. To further appreciate the impact of this methodology, the authors discuss some recent examples of clinical candidates that utilize key cross-coupling reactions in their large-scale synthetic process. Looking into future opportunities, the authors highlight the versatility of the cross-coupling reactions towards new chemical modalities like DNA-encoded libraries (DELs), new generation of peptides and cyclopeptides, allosteric modulators, and proteolysis targeting chimera (PROTAC) approaches.
We present observations of transverse oscillations in slender Ca ii H fibrils (SCFs) in the lower solar chromosphere. We use a 1 hr long time series of high- (spatial and temporal-) resolution ...seeing-free observations in a 1.1 Å wide passband covering the line core of Ca ii H 3969 Å from the second flight of the Sunrise balloon-borne solar observatory. The entire field of view, spanning the polarity inversion line of an active region close to the solar disk center, is covered with bright, thin, and very dynamic fine structures. Our analysis reveals the prevalence of transverse waves in SCFs with median amplitudes and periods on the order of 2.4 0.8 km s−1 and 83 29 s, respectively (with standard deviations given as uncertainties). We find that the transverse waves often propagate along (parts of) the SCFs with median phase speeds of 9 14 km s−1. While the propagation is only in one direction along the axis in some of the SCFs, propagating waves in both directions, as well as standing waves are also observed. The transverse oscillations are likely Alfvénic and are thought to be representative of magnetohydrodynamic kink waves. The wave propagation suggests that the rapid high-frequency transverse waves, often produced in the lower photosphere, can penetrate into the chromosphere with an estimated energy flux of 15 kW m−2. Characteristics of these waves differ from those reported for other fibrillar structures, which, however, were observed mainly in the upper solar chromosphere.
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