Short-term traffic forecast is one of the essential issues in intelligent transportation system. Accurate forecast result enables commuters make appropriate travel modes, travel routes, and departure ...time, which is meaningful in traffic management. To promote the forecast accuracy, a feasible way is to develop a more effective approach for traffic data analysis. The availability of abundant traffic data and computation power emerge in recent years, which motivates us to improve the accuracy of short-term traffic forecast via deep learning approaches. A novel traffic forecast model based on long short-term memory (LSTM) network is proposed. Different from conventional forecast models, the proposed LSTM network considers temporal–spatial correlation in traffic system via a two-dimensional network which is composed of many memory units. A comparison with other representative forecast models validates that the proposed LSTM network can achieve a better performance.
Methane monooxygenases (MMOs) mediate the facile conversion of methane into methanol in methanotrophic bacteria with high efficiency under ambient conditions. Because the selective oxidation of ...methane is extremely challenging, there is considerable interest in understanding how these enzymes carry out this difficult chemistry. The impetus of these efforts is to learn from the microbes to develop a biomimetic catalyst to accomplish the same chemical transformation. Here, we review the progress made over the past two to three decades toward delineating the structures and functions of the catalytic sites in two MMOs: soluble methane monooxygenase (sMMO) and particulate methane monooxygenase (pMMO). sMMO is a water-soluble three-component protein complex consisting of a hydroxylase with a nonheme diiron catalytic site; pMMO is a membrane-bound metalloenzyme with a unique tricopper cluster as the site of hydroxylation. The metal cluster in each of these MMOs harnesses O2 to functionalize the CH bond using different chemistry. We highlight some of the common basic principles that they share. Finally, the development of functional models of the catalytic sites of MMOs is described. These efforts have culminated in the first successful biomimetic catalyst capable of efficient methane oxidation without overoxidation at room temperature.
Programmable gene-editing tools have transformed the life sciences and have shown potential for the treatment of genetic disease. Among the CRISPR-Cas technologies that can currently make targeted ...DNA changes in mammalian cells, prime editors offer an unusual combination of versatility, specificity and precision. Prime editors do not require double-strand DNA breaks and can make virtually any substitution, small insertion and small deletion within the DNA of living cells. Prime editing minimally requires a programmable nickase fused to a polymerase enzyme, and an extended guide RNA that both specifies the target site and templates the desired genome edit. In this Review, we summarize prime editing strategies to generate programmed genomic changes, highlight their limitations and recent developments that circumvent some of these bottlenecks, and discuss applications and future directions.
The enumeration and characterization of circulating tumor cells (CTCs), found in the peripheral blood of cancer patients, provide a potentially accessible source for cancer diagnosis and prognosis. ...This work reports on a novel spiral microfluidic device with a trapezoidal cross-section for ultra-fast, label-free enrichment of CTCs from clinically relevant blood volumes. The technique utilizes the inherent Dean vortex flows present in curvilinear microchannels under continuous flow, along with inertial lift forces which focus larger CTCs against the inner wall. Using a trapezoidal cross-section as opposed to a traditional rectangular cross-section, the position of the Dean vortex core can be altered to achieve separation. Smaller hematologic components are trapped in the Dean vortices skewed towards the outer channel walls and eventually removed at the outer outlet, while the larger CTCs equilibrate near the inner channel wall and are collected from the inner outlet. By using a single spiral microchannel with one inlet and two outlets, we have successfully isolated and recovered more than 80% of the tested cancer cell line cells (MCF-7, T24 and MDA-MB-231) spiked in 7.5 mL of blood within 8 min with extremely high purity (400-680 WBCs mL(-1); ~4 log depletion of WBCs). Putative CTCs were detected and isolated from 100% of the patient samples (n = 10) with advanced stage metastatic breast and lung cancer using standard biomarkers (CK, CD45 and DAPI) with the frequencies ranging from 3-125 CTCs mL(-1). We expect this simple and elegant approach can surmount the shortcomings of traditional affinity-based CTC isolation techniques as well as enable fundamental studies on CTCs to guide treatment and enhance patient care.
Conspectus When molecules transition from the condensed phase to the gas phase, their spectra undergo a dramatic transformation as well; each peak in a condensed-phase spectrum can yield thousands of ...peaks in the gas phase because the molecules are free to rotate and those rotational motions are quantized. These gas-phase spectra contain a wealth of detailed information about molecular structure and behavior, but peak densities are often so high that congestion obscures the patterns needed to assign peaks and extract molecular constants. This Account describes how coherent multidimensional techniques not only reduce peak densities and congestion in gas-phase spectra but also create multidimensional patterns that are easy to recognize and interpret. First, all peaks with the same vibrational quantum numbers form rotational patterns such as X’s, double parabolas, and asterisks. These rotational patterns are composed of basic units and can provide immediate information about the molecule’s structure, behavior, and rotational selection rules. Second, groups of these rotational patterns can be arranged into vibrational patterns that form arrays of rectangles or parallelograms. These vibrational patterns can be used to determine wave-mixing processes and measure vibrational constants. Coherent multidimensional spectroscopy therefore automatically separates vibrational and rotational information and then sorts peaks by vibrational and rotational quantum number. Furthermore, if the sample is composed of a mixture, then these patterns can also sort peaks by species, and higher-dimensional techniques can even provide the ability to select a species in the mixture. These techniques have successfully produced highly patterned 2D and 3D spectra for samples that otherwise generate patternless spectra such as isotopologue mixtures and vibronically perturbed molecules such as NO2. High densities of states can lead to congestion and perturbations that make it difficult to accurately assign peaks using the information that is traditionally available from 1D spectra: a peak’s intensity and its frequency. Coherent 2D and 3D techniques are well-suited for dealing with and learning from perturbations because the coordinate of each peak in multidimensional space includes multiple frequency values. Accurate assignments are possible when peaks in 2D or 3D spectra that are perturbed along one frequency axis are unperturbed along an orthogonal frequency axis. Furthermore, patterns often repeat in adjacent rows or columns, so regions that are less congested can be used to resolve or identify key peaks or patterns in regions that are severely congested. Perturbations can make the spacings within multidimensional rotational and vibrational patterns slightly irregular, but these automatically generated patterns remain easy to recognize and analyze. This Account describes three high-resolution coherent multidimensional spectroscopy techniques, the types of patterns they can produce, and how information can be extracted from these patterns. This work is being conducted at Spelman College, a historically Black college for women where all of the students are undergraduates. The resulting techniques are not only highly effective for dealing with some of the most congested, perturbed, and challenging spectroscopic systems, but they are relatively easy to use, moderate in price to set up, and quick to run.
•Difference in phenolic content and composition of quinoa seeds of different colour.•Identification of free and conjugated phenolics by LC–ESI-MS.•First report of the identification of betacyanins in ...red and black quinoa.•Phenolic compounds contribute significantly to the antioxidant activities.•Darker quinoa seeds had higher levels of phenolics and antioxidant activities.
Quinoa (Chenopodium quinoa Willd.) is known for its exceptional nutritional value and potential health benefits. The present study identified the composition of different forms of extractable phenolics and betacyanins of quinoa cultivars in white, red and black, and how they contribute to antioxidant activities. Results showed that at least 23 phenolic compounds were found in either free or conjugated forms (liberated by alkaline and/or acid hydrolysis); the majority of which were phenolic acids, mainly vanillic acid, ferulic acid and their derivatives as well as main flavonoids quercetin, kaempferol and their glycosides. Betacyanins, mainly betanin and isobetanin, were confirmed for the first time to be the pigments of the red and black quinoa seeds, instead of anthocyanins. Darker quinoa seeds had higher phenolic concentration and antioxidant activity. Findings of these phenolics, along with betacyanins in this study add new knowledge to the functional components of quinoa seeds of different cultivar background.
While prime editing enables precise sequence changes in DNA, cellular determinants of prime editing remain poorly understood. Using pooled CRISPRi screens, we discovered that DNA mismatch repair ...(MMR) impedes prime editing and promotes undesired indel byproducts. We developed PE4 and PE5 prime editing systems in which transient expression of an engineered MMR-inhibiting protein enhances the efficiency of substitution, small insertion, and small deletion prime edits by an average 7.7-fold and 2.0-fold compared to PE2 and PE3 systems, respectively, while improving edit/indel ratios by 3.4-fold in MMR-proficient cell types. Strategic installation of silent mutations near the intended edit can enhance prime editing outcomes by evading MMR. Prime editor protein optimization resulted in a PEmax architecture that enhances editing efficacy by 2.8-fold on average in HeLa cells. These findings enrich our understanding of prime editing and establish prime editing systems that show substantial improvement across 191 edits in seven mammalian cell types.
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•Pooled CRISPRi screens reveal that MMR inhibits prime editing efficiency and precision•PE4 and PE5 enhance editing outcomes through co-expression of dominant negative MLH1•Programming additional silent mutations can enhance prime editing by evading MMR•PEmax editor improves prime editing efficacy in synergy with PE4, PE5, and epegRNAs
PE4 and PE5 are efficient and precise prime editing systems developed by leveraging insights into the way DNA repair pathways impact genome editing outcomes
London dispersion, universally attractive forces originating from fluctuating dipoles, is omnipresent in molecules. While its understanding has recently made tremendous progress, its general ...appreciation is still lagging behind electrostatics. This can be explained by the simple tools available to study electrostatic interactions, such as electrostatic potential (ESP) maps and partial charges, and a lack thereof for dispersion. We herein report a universal quantitative descriptor of dispersion interaction potentials, which allows assessing dispersion visually by London dispersion potential (LDP) maps, and quantitatively using the average LDP on the van der Waals surface. We demonstrate the utility of these new tools by constructing a quantitative dispersion energy scale of the elements and common substituents, studying non‐covalent interactions (NCIs), and developing modern linear free energy relationships in catalysis.
A map of London: A new descriptor of the quantitative dispersion interaction potential is introduced and applied to the study of non‐covalent interactions in spectroscopy, nanomaterials, and catalysis. It allows the generation of London dispersion potential maps indicating the site of strongest dispersion and the estimation of average dispersion interaction strengths of any atom or molecule.
Prime editing enables the installation of virtually any combination of point mutations, small insertions or small deletions in the DNA of living cells. A prime editing guide RNA (pegRNA) directs the ...prime editor protein to the targeted locus and also encodes the desired edit. Here we show that degradation of the 3' region of the pegRNA that contains the reverse transcriptase template and the primer binding site can poison the activity of prime editing systems, impeding editing efficiency. We incorporated structured RNA motifs to the 3' terminus of pegRNAs that enhance their stability and prevent degradation of the 3' extension. The resulting engineered pegRNAs (epegRNAs) improve prime editing efficiency 3-4-fold in HeLa, U2OS and K562 cells and in primary human fibroblasts without increasing off-target editing activity. We optimized the choice of 3' structural motif and developed pegLIT, a computational tool to identify non-interfering nucleotide linkers between pegRNAs and 3' motifs. Finally, we showed that epegRNAs enhance the efficiency of the installation or correction of disease-relevant mutations.
Perfluoroalkanes are considered generally to have weak inter- and intramolecular forces compared to alkanes, explaining their relatively low boiling points, low surface tensions, and poor solvent ...properties. However, currently accepted models do not satisfactorily explain several trends in their properties-for instance, boiling point trends as size increases. Herein, we report a comprehensive computational study of the intermolecular interactions of alkanes and perfluoroalkanes, demonstrating that perfluoroalkanes have a higher intrinsic ability for dispersive interactions than their alkane counterparts and that dispersion in perfluoroalkane dimers mainly stems from fluorine-fluorine interactions. In addition, the reasons for relatively weak intermolecular forces in perfluoroalkanes compared to alkanes are their ground-state geometries, which are increasingly unsuitable for intermolecular interactions as the carbon chain length increases, and their rigidity, which makes deformation from the ground-state geometries unfavorable. Overall, these trends are reflected in a dependence of the bulk properties of perfluoroalkanes on the carbon chain length as the fluorine content decreases and the interaction geometries become increasingly unsuitable.
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