An undesirable sensory attribute (“floral taint”) has recently been detected in red wines from some winegrowing jurisdictions in North America (e.g., Ontario, British Columbia, Washington), caused by the introduction of frost-killed leaves and petioles [materials-other-than-grapes (MOG)] during mechanical harvest and winemaking. It was hypothesized that terpenes, norisoprenoids, and higher alcohols would be the main responsible compounds. The objectives were to investigate the causative volatile compounds for floral taint and explore threshold concentrations for this problem. Commercial wines displaying varying intensities of floral taint were subjected to GC-MS and sensory analysis. Several odor-active compounds were higher in floral-tainted wines, including terpenes (geraniol, citronellol, cis- and trans-rose oxide), norisoprenoids (β-damascenone, β-ionone), five ethyl esters, and three alcohols. Thereafter, fermentations of Cabernet Franc (CF) and Cabernet Sauvignon (CS) (2016, 2017) were conducted. MOG treatments were (w/w): 0, 0.5%, 1%, 2%, and 5% petioles, and 0, 0.25%, 0.5%, 1%, and 2% leaf blades. Terpenes (linalool, geraniol, nerol, nerolidol, citronellol, citral, cis- and trans-rose oxides, eugenol, myrcene), norisoprenoids (α- and β-ionone), and others (e.g., hexanol, octanol, methyl and ethyl salicylate) increased linearly/quadratically with increasing MOG levels in both cultivars. Principal components analysis separated MOG treatments from the controls, with 5% petioles and 2% leaves as extremes. Increasing MOG levels in CF wines increased floral aroma intensity, primarily associated with terpenes, higher alcohols, and salicylates. Increased leaf levels in CF were associated with higher vegetal and earthy attributes. Increased petioles in CS were not correlated with floral aromas, but increased leaves increased floral, vegetal, and herbaceous attributes. Overall, petioles contributed more to floral taint than leaves through increased terpenes and salicylates (floral notes), while leaves predominantly contributed norisoprenoids and C6 alcohols (green notes).

Accurate measurement of plant transpiration is critical to gaining a better understanding of plant water use and exploration of the influence of plants on regional and even global climate. Heat tracer-based sap flow (HTSF) techniques are currently the dominant method to estimate plant transpiration at the individual plant level. However, the majority of current research focuses on specific applications or the evaluation of the method itself, and there is a lack of an overall analysis of HTSF methods. The objectives of this study were: (i) to briefly review the theories and categories of the various HTSF methods, and (ii) to undertake a bibliometric analysis of the use of HTSF methods in measuring plant transpiration. Each HTSF method is described mathematically and their application and pros and cons are briefly discussed. A bibliometric analysis was conducted using 3964 papers published between 1992 and 2020 archived in the Web of Science core collection. The analysis identified publication trends, the most productive authors, organizations, and countries, as well as the most utilized HTSF method (i.e., thermal dissipation) and journals in which these papers were published. In addition, world distribution maps of the use of HTSF methods and tree species measured were drawn based on 741 selected publications with in situ measurements.

“Floral taint”, a unique sensory defect that has been detected in red wines in North America, is caused by frozen leaves and petioles (materials other than grapes; MOG) introduced during mechanical harvest. Responsible volatiles are likely terpenes, norisoprenoids, and esters. Objectives of this study were to investigate volatile compounds that may cause floral taint and to evaluate yeast strains that could mitigate the problem for a series of different leaf- and petiole-based MOG levels. Replicate Cabernet franc fermentations (2017 to 2019) combined MOG treatments ([wt/wt]: 0, 0.5%, and 2% leaf blades, and 0, 1%, and 5% petioles) with three yeast strains (CSM, EC1118, and FX10). Increases in leaf and petiole levels resulted in primarily linear increases in many aroma compounds, particularly terpenes. Increases in leaf addition increased concentrations of nine (2017), 12 (2018), or 17 terpenes (2019). Increased petioles led to linear increases in 13 (2017), 12 (2018), or 15 terpenes (2019). Norisoprenoids and salicylates were also responsive. Yeast effects varied with leaf and petiole levels and with season. Fermentations with 2% leaves displayed yeast-related differences in nine, four, and 10 terpenes, and four, two, and nine esters in 2017, 2018, and 2019, respectively. Fermentations with 5% petioles displayed yeast-related differences in three, six, and eight terpenes, and three, two, and five esters in 2017, 2018, and 2019, respectively. Yeasts EC1118 and FX10 produced the least terpenes at all leaf and petiole levels, while CSM produced the most. Results suggest that incorporation of frozen MOG to fermentations will result in elevated concentrations of terpenes, norisoprenoids, and salicylates associated with floral taint, and that specific yeast strains may diminish this problem.

An undesirable sensory attribute ("floral taint") has been detected in red wines in North America, caused by leaves and petioles (materials other than grapes [MOG]) introduced during mechanical harvest after killing frosts. From 2017 to 2019, several harvest strategies were evaluated on Ontario Cabernet franc: hand harvest (HH), conventional machine harvesting (MECH), Braud-New Holland Opti (OPTI), Gregoire GL8, MECH + optical sorting (MECH+OS), and MECH with preharvest leaf removal (MECH+BLR). Concentrations of 41 odor-active compounds were quantified by gas chromatography-mass spectrometry. Harvest treatment effects varied by season. In 2017, HH resulted in lowest ethyl isobutyrate (MECH+BLR), ethyl nonoate, cis-linalool oxide (plus MECH and OPTI), trans-linalool oxide (plus MECH+OS), β-citral, and cis- and trans-rose oxide (plus MECH and OPTI). Ethyl hexanoate was lowest in MECH, and MECH+BLR, isoamyl hexanoate was lowest in all treatments except HH, and α-ionone was lowest in MECH and MECH+BLR. In 2018, HH resulted in the lowest β-damascenone, ethyl salicylate (plus OPTI and Gregoire), citronellol (plus Gregoire), cis- and trans-rose oxide (plus Gregoire), and eugenol (plus Gregoire). Isobutyl acetate, isoamyl hexanoate, and nerol were additionally reduced by Gregoire, and isopropylmethoxypyrazine was reduced by all treatments except HH. In 2019, harvest strategy affected 27 of 41 compounds, including 11 esters and 12 terpenes. Treatments leading to lowest concentrations were HH (nine compounds), MECH (eight compounds), MECH+BLR (10 compounds), OPTI (21 compounds), Gregoire (10 compounds), and MECH+OS (22 compounds). Wines from fruit that had undergone a killing frost contained different concentrations of 14 and eight compounds (2018), and 17 and 13 compounds (2019) for Cabernet franc and Cabernet Sauvignon, respectively. Results suggest that specific harvest technologies can reduce MOG and associated increases in aroma compounds, although seasonal differences may occur.

Recently, attention based encoder-decoder methods have been widely used in online handwritten mathematical expression recognition, which achieve significant improvements compared to traditional methods. The encoder-decoder methods usually employ string decoders to generate the recognition result, which are not well matched for tree-structured languages like math expression. A novel sequential relation decoder (SRD) was introduced to recognize the online mathematical expression as a math tree, which can be decomposed into a subtree sequence and each subtree consists of a relation node and two symbol nodes (related symbol node and primary symbol node). However, the alignments between these two symbol nodes were implemented by spatial attention probabilities, leading to incorrect recognition if spatial attention is not accurate. In this paper, we propose a memory relation decoder (MRD), equipped with a memory based attention model to determine the correspondence between two symbol nodes. Specifically, at each decoding step, this memory based attention finds the corresponding primary symbol node in the memory and treats it as the related symbol node, which actually achieves the alignments between two symbol nodes in an explicit manner. Besides, we propose to introduce global visual information while calculating attention probabilities to help alleviate the ambiguous problems in online handwritten mathematical expression recognition. Evaluated on a benchmark published by CROHME competition, the proposed approach can substantially outperform previous encoder-decoder methods.

Significance Our study demonstrates that CD34 + cells generated from human induced pluripotent stem cells (iPSCs) genetically engineered to confer resistance to HIV have engraftment capabilities if they are derived in vivo but not in vitro. We used iPSCs from HIV-infected patients under antiretroviral therapy to form teratomas in immunodeficient mice and isolated CD34 + cells from these teratomas. We showed not only that these CD34 + cells could engraft in recipient mice but also that their cell progeny found in the mouse peripheral blood was resistant to HIV infection. These findings confirm the potential for evaluating in an animal model the clinical development of cure therapies using genetically modified autologous iPSCs from patients with HIV.

OBJECTIVES:The discovery of induced pluripotent stem cells (iPSC) has brought promise to regenerative medicine as it breaks the ethical barrier of using embryonic stem cells. Such cell culture-derived patient-specific autologous stem cells are needed for transplantation. Here we report deriving HIV-1-infected patients' iPSC lines under transgene-free methods and under feeder-free and xeno-free culture conditions to meet the requirement for clinical application.METHODS AND RESULTS:We have reprogrammed patients' peripheral blood mononuclear cells with EBNA1/OriP episomal vectors, or a defective and persistent Sendai virus vector (SeVdp) to ensure a nonintegrating iPSC generation. Both single picked and pooled iPSC lines demonstrated high pluripotency and were able to differentiate into various lineage cells in vivo. The established cell lines could be modified by genetic editing using the TALENs or CRISPR/Cas 9 technology to have a bi-allelic CCR5Δ32 mutations seamlessly. All generated iPSC lines and modified cell lines had no evidence of HIV integration and maintained normal karyotype after expansion.CONCLUSIONS:This study provides a reproducible simple procedure for generating therapeutic grade iPSCs from HIV-infected patients and for engineering these cells to possess a naturally occurring genotype for resistance to HIV-1 infection when differentiated into immune cells.

SummaryHereditary persistence of fetal haemoglobin (HPFH) is the major modifier of the clinical severity of β‐thalassaemia. The homozygous mutation c.‐196 C>T in the Aγ‐globin (HBG1) promoter, which causes Sardinian δβ0‐thalassaemia, is able to completely rescue the β‐major thalassaemia phenotype caused by the β039‐thalassaemia mutation, ensuring high levels of fetal haemoglobin synthesis during adulthood. Here, we describe a CRISPR/Cas9 genome‐editing approach, combined with the non‐homologous end joining (NHEJ) pathway repair, aimed at reproducing the effects of this naturally occurring HPFH mutation in both HBG promoters. After selecting the most efficient guide RNA in K562 cells, we edited the HBG promoters in human umbilical cord blood‐derived erythroid progenitor 2 cells (HUDEP‐2) and in haematopoietic stem and progenitor cells (HSPCs) from β0‐thalassaemia patients to assess the therapeutic potential of HbF induction. Our results indicate that small deletions targeting the −196‐promoter region restore high levels of fetal haemoglobin (HbF) synthesis in all cell types tested. In pools of HSPCs derived from homozygous β039‐thalassaemia patients, a 20% editing determined a parallel 20% increase of HbF compared to unedited pools. These results suggest that editing the region of HBG promoters around the −196 position has the potential to induce therapeutic levels of HbF in patients with most types of β‐thalassaemia irrespective of the β‐globin gene (HBB) mutations.

Objective: To assess the in-vitro CCR5---tropic and CXCR4---tropic HIV---1 infectivity of immune cells, particularly macrophages, derived fromCCR5 gene---edited induced pluripotent stem cells (iPSCs) obtained from the peripheral blood mononuclear cells (PBMC) of HIV---infected patients on antiretroviral therapy (ART). Design: PBMC were obtained from six patients who had been HIV---infected for over 20 years and were on ART for 1---12 years prior to this study. Methods: The PBMC were derived into iPSCs and genetically edited with TALENs or CRISPR---cas9 endonucleases combined with PiggyBac technology to introduce the naturally occurring 32---bp deletion to theCCR5 gene. These iPSCs were differentiated into macrophages, and subsequently challenged with CCR5---tropic or CCR5/CXCR4 dual--- tropic HIV---1 strains. iPSC derivation, gene editing and immune cell differentiation were done in feeder---free, xeno---free in-vitro conditions. Results: Multiple unedited (wild---type) andCCR5 gene---edited (mutant) iPSCs were derived from patients' PBMC. When differentiated into immune cells and HIV---1 challenged, mutant iPSC lines were resistant to CCR5---tropic and to some extent to CCR5/CXCR4 dual---tropic HIV---1 infection when compared to wild---type iPSC lines. Conclusion: Our study demonstrates that iPSC---derived, gene---edited immune cells are resistant to distinct HIV---1 strains. These findings have important implications for both in-vitro stem cell development and therapeutic approaches to cure HIV infection.

高比例可再生能源并网是未来电力系统的发展趋势,输电网规划方案综合评价应该契合高比例可再生能源并网的新特点.首先介绍了输电网规划方案综合评价的基本要素和评价流程,并从评价指标体系和综合评价方法两个角度对现有的电网规划评价相关研究进行了综述.然后从可再生能源的强不确定性、可再生能源消纳压力、高度电力电子化与交直流混联等三个方面分析了高比例可再生能源并网对输电网规划评价与决策的影响.在此基础上,从评价对象、评价指标、评价方法以及评价结果的应用等四个维度对未来面向高比例可再生能源并网的输电网规划方案综合评价研究进行了展望.

Freezing-thawing events contribute to the unique aroma profile of icewines. Differences in key odor-active volatile compounds between 'Beibinghong' (Vitis amurensis × V. vinifera) icewines and dry wines were investigated by gas chromatography-olfactometry and gas chromatography-mass spectrometry. Acceptable agreement between the olfactometric and quantitative results was obtained. 'Beibinghong' icewine was characterized by high concentrations of volatile phenols, lactones, (E)-β-damascenone, and phenylacetaldehyde, which were associated with on-vine freezing-thawing events in grape. Low concentrations of higher alcohol acetates and ethyl esters of fatty acids were attributed to hyperosmotic stress during fermentation. The overall aroma of icewine could be mimicked by reconstitution containing 44 identified volatiles. Partial least squares regression analysis demonstrated that the concentrations of these volatile compounds determined the distinct sensory profiles of icewines, which have higher intensities of honey/sweet, smoky, caramel, dried fruit, apricot/peach, and floral aromas, and lower intensities of fresh fruity and herbaceous notes in comparison with dry wines.

Derivation of human hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) offers considerable promise for cell therapy, disease modeling, and drug screening. However, efficient derivation of functional iPSC-derived HSCs with in vivo engraftability and multilineage potential remains challenging. Here, we demonstrate a tractable approach for respecifying iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells (HSPCs) through transient expression of a single transcription factor, MLL-AF4 . These induced HSPCs (iHSPCs) derived from iPSCs are able to fully reconstitute the human hematopoietic system in the recipient mice without myeloid bias. iHSPCs are long-term engraftable, but they are also prone to leukemic transformation during the long-term engraftment period. On the contrary, primary HSPCs with the same induction sustain the long-term engraftment without leukemic transformation. These findings demonstrate the feasibility of activating the HSC network in human iPSC-derived blood cells through expression of a single factor and suggest iHSPCs are more genomically instable than primary HSPCs, which merits further attention.

目前我国西电东送的规模正在逐步扩大,西部地区可再生能源装机逐渐增加,未来将接入高比例风电与光伏发电。具有较强随机性和间歇性可再生能源需要灵活性机制进行调节,传统方案是与火电打捆外送。而西南地区已有大量水电,西北西南地区进行大规模互联,能够实现不同形式电源的时空互补,从而在更大范围内消纳可再生能源并提升西电东送线路的容量效益。采用时序运行模拟技术论证了我国西北-西南联网的优势与联网效益。采用西北-西南送端电网2030年规划方案进行实证分析,结果表明西北-西南联网能够有效降低可再生能源弃电比例,并指出西北-西南联网通道合理规模在90～100 GW之间,在送电时序特性方面,西北-西南联网有助于减小西南水电外送的季节波动性,向东部送电曲线采用正调峰（8:00—19:00为峰荷时段,其余时间为非峰荷时段）将有利于可再生能源的消纳。

This paper proposes a multi-objective optimal planning model of access location and access capacity for large-scale integrated wind power generation considering the mutual restriction between the planning of large-scale wind power plants and the planning of power system network. In this model, the power flow equilibrium degree, investment costs and active network loss are taken as the optimization goals. The improved differential evolution (IDE) algorithm is applied to calculate the Pareto optimal solution set of wind power's access planning. With the solution results described by the Pareto pattern, all the alternative solutions are then ranked based on the entropy weight method and the final compromised solution is selected by the method of technique for order preference by similarity to ideal (TOPSIS). And the proposed optimal planning model is tested based on a practical planning need of large-scale integrated wind power generation in an actual power grid of China in 2020. The simulation results show that applied with the proposed optimization model and matching algorithm, the planning scheme of large-scale wind power's access location and access capacity under complex and practical power system circumstances has been successfully optimized.

Chardonnay is a neutral grape variety offering a diversity of wine styles that are popular among consumers. The links between wine production methods and Chardonnay wine volatile composition, as determinants of quality, require further elucidation. Over 80 commercial Australian Chardonnay wines were assessed by expert panelists who were asked to define four distinct levels of quality in a blind tasting. Wine aroma volatiles in each wine were analyzed by solid-phase microextraction-gas chromatography-mass spectrometry, and multivariate statistical techniques were used to examine the relationship between volatile composition and quality as defined by the experts. Of 39 aroma compounds quantified, nine volatiles (including cis- and trans-oak lactones, furfural, and diethyl succinate) correlated significantly and positively with Chardonnay wine quality, while 11 volatiles (including fruity esters and monoterpenoids) correlated negatively. Compounds associated with oak contact and malolactic fermentation were present at highest concentrations in higher-quality wines as perceived by wine experts. Lower scores were assigned to younger but less complex wines, which were richer in fruity esters and other grape-derived compounds. A model was developed using partial least squares regression based on these results, which permitted classification of the Chardonnay wines into high-, medium-, and low-quality brackets depending on their relative concentrations of cis- and trans-oak lactone, ethyl lactate, and 2-methyl-1-propanol (positive) and of 1-propanol and 1-hexanol (negative). There was a significant and positive correlation (r = 0.469, p < 0.0001) between retail price and quality score, underlying the usefulness of price as an indicator of quality, although it failed to entirely explain quality (as judged by experts) and should therefore be used in conjunction with other quality cues.

With the rapid development of wind power and the increasing degree of grid interconnection, the structure of power grid is becoming more and more complicated, and the operation mode is also more diversified. Some small disturbances may lead to cascading failure, or even collapse of grid. So it is important to study on cascading failure of complex grid. In this paper, the power model of wind power is first established, and the brittleness is used to evaluate the risk of brittle chain of cascading failure from two aspects: probability and severity. The brittle chain with high risk is forecasted. Then a method of early warning for cascading failure with power grid integration is proposed. Finally, the feasibility and effectiveness of the early warning method are verified by IEEE 30-node example with wind farm. This method provides support for early warning of cascading failures.

In the most current methods of probabilistic power system production simulation, the output characteristics of new energy power generation (NEPG) has not been comprehensively considered. In this paper, the power output characteristics of wind power generation and photovoltaic power generation are firstly analyzed based on statistical methods according to their historical operating data. Then the characteristic indexes and the filtering principle of the NEPG historical output scenarios are introduced with the confidence level, and the calculation model of NEPG’s credible capacity is proposed. Based on this, taking the minimum production costs or the best energy-saving and emission-reduction effect as the optimization objective, the power system operation model with large-scale integration of new energy power generation (NEPG) is established considering the power balance, the electricity balance and the peak balance. Besides, the constraints of the operating characteristics of different power generation types, the maintenance schedule, the load reservation, the emergency reservation, the water abandonment and the transmitting capacity between different areas are also considered. With the proposed power system operation model, the operation simulations are carried out based on the actual Northwest power grid of China, which resolves the new energy power accommodations considering different system operating conditions. The simulation results well verify the validity of the proposed power system operation model in the accommodation analysis for the power system which is penetrated with large scale NEPG.

Fibroblasts can be transdifferentiated directly into other somatic cells such as cardiomyocytes, hematopoietic cells, and neurons. An advantage of somatic cell differentiation without first generating induced pluripotent stem cells (iPSCs) is that it avoids contamination of the differentiated cells with residual iPSCs, which may cause teratoma. However, since primary fibroblasts from biopsy undergo senescence during repeated culture, it may be difficult to grow transdifferentiated cells in sufficient numbers for future therapeutic purposes. To circumvent this problem, we reversibly immortalized primary fibroblasts by using the piggyBac transposon to deliver the human telomerase reverse transcriptase (hTERT) gene hTERT plus SV40 Large T. Both approaches enabled fibroblasts to grow continuously without senescence, and neither caused teratoma formation in immunodeficient mice. However, fibroblasts immortalized with hTERT plus SV40 large T antigen accumulated chromosomal rearrangements, whereas fibroblasts immortalized with hTERT retained the normal karyotype. To transdifferentiate hTERT-immortalized fibroblasts into other somatic lineage cells, we transiently transfected them with episomal OCT4 and cultured them under neural cell growth condition with transposase to remove the transposon. Tripotent neural progenitor cells were seamlessly and efficiently generated. Thus, reversible immortalization of primary fibroblasts with hTERT will allow potential autologous cell-based therapeutics that bypass and simulate iPSC generation.