Miracle-dz/UniFAR-FTUs huggingface dataset:
i‐GONAD: A method for generating genome‐edited animals without ex vivo handling of embryos

The recent development of genome editing technologies has enabled the creation of genome‐edited animals, with alterations at the desired target locus. The clustered regularly interspaced short palindromic repeats (CRISPR) system is widely used for this purpose because it is simpler and more efficient than other genome editing technologies. The conventional methods for creation of genome‐edited animals involve ex vivo handling of embryos (zygotes) for microinjection or in vitro electroporation. However, this process is laborious and time‐consuming, and relatively large numbers of animals are used. Furthermore, these methods require specialized skills for handling embryos. In 2015, we reported a novel method for the creation of genome‐edited animals without ex vivo handling of embryos. The technology known as Genome‐editing via Oviductal Nucleic Acids Delivery (GONAD) involved intraoviductal instillation of genome editing components into a pregnant female and subsequent in vivo electroporation of an entire oviduct. The genome editing components present in the oviductal lumen are transferred to preimplantation embryos in situ for introducing insertion or deletion (indel) mutations at the desired loci. This technology was further improved by optimizing several parameters to develop improved GONAD (i‐GONAD) for the efficient generation of mutant or knock‐in animals. In this review, we discuss the historical background, potential applications, advantages, and future challenges of GONAD/i‐GONAD technology.
Developing heritable mutations in Arabidopsis thaliana using a modified CRISPR/Cas9 toolkit comprising PAM-altered Cas9 variants and gRNAs.

CRISPR/Cas9, comprising an RNA-guided DNA endonuclease and a programmable guide RNA (gRNA), is currently recognized to be a powerful genome-editing tool and is widely used in biological science. Despite the usefulness of the system, a protospacer-adjacent motif (PAM) immediately downstream of the target sequence needs to be taken into account in the design of the gRNA, a requirement which limits the flexibility of the CRISPR-based genome editing system. To overcome this limitation, a Cas9 isolated from Streptococcus pyogenes, namely SpCas9, engineered to develop several variants of Cas9 nuclease, has been generated. SpCas9 recognizes the NGG sequence as the PAM, whereas its variants are capable of interacting with different PAMs. Despite the potential advantage of the Cas9 variants, their functionalities have not previously been tested in the widely used model plant, Arabidopsis thaliana. Here, we developed a plant-specific vector series harboring SpCas9-VQR (NGAN or NGNG) or SpCas9-EQR (NGAG) and evaluated their functionalities. These modified Cas9 nucleases efficiently introduced mutations into the CLV3 and AS1 target genes using gRNAs that were compatible with atypical PAMs. Furthermore, the generated mutations were passed on to their offspring. This study illustrated the usefulness of the SpCas9 variants because the ability to generate heritable mutations will be of great benefit in molecular genetic analyses. A greater number of potential SpCas9-variant-recognition sites in these genes are predicted, compared with those of conventional SpCas9. These results demonstrated the usefulness of the SpCas9 variants for genome editing in the field of plant science research.
Why does allometry evolve so slowly?

Morphological allometry is striking due to its evolutionary conservatism, making it an example of a certain sort of evolutionary stasis. Organisms that vary in size, whether for developmental, environmental or evolutionary reasons, adopt shapes that are predictable from that size alone. There are two major hypotheses to explain this. It may be natural selection strongly favors each allometric pattern, or that organisms lack the development and genetic capacity to produce variant shapes for selection to act on. Using a high-throughput system for measuring the size and shape of Drosophila wings, we documented an allometric pattern that has been virtually unchanged for 40 million years. We performed an artificial selection experiment on the static allometric slope within one species. In just 26 generations, we were able to increase the slope from 1.1 to 1.4, and decrease it to 0.8. Once artificial selection was suspended, the slope rapidly evolved back to a value near the initial static slope. This result decisively rules out the hypothesis that allometry is preserved due to a lack of genetic variation, and provides evidence that natural selection acts to maintain allometric relationships. On the other hand, it seems implausible that selection on allometry in the wing alone could be sufficiently strong to maintain static allometries over millions of years. This suggests that a potential explanation for stasis is selection on a potentially large number of pleiotropic effects. This seems likely in the case of allometry, as the sizes of all parts of the body may be altered when the allometric slope of one body part is changed. Unfortunately, hypotheses about pleiotropy have been very difficult to test. We lay out an approach to begin the systematic study of pleiotropic effects using genetic manipulations and high-throughput phenotyping.
A xylem‐produced peptide PtrCLE20 inhibits vascular cambium activity in Populus

Summary In trees, lateral growth of the stem occurs through cell divisions in the vascular cambium. Vascular cambium activity is regulated by endogenous developmental programmes and environmental cues. However, the underlying mechanisms that regulate cambium activity are largely unknown. Genomic, biochemical and genetic approaches were used here to elucidate the role of PtrCLE20, a CLAVATA3 (CLV3)/embryo surrounding region (ESR)‐related peptide gene, in the regulation of lateral growth in Populus. Fifty‐two peptides encoded by CLE genes were identified in the genome of Populus trichocarpa. Among them PtrCLE20 transcripts were detected in developing xylem while the PtrCLE20 peptide was mainly localized in vascular cambium cells. PtrCLE20 acted in repressing vascular cambium activity indicated by that upregulation of PtrCLE20 resulted in fewer layers of vascular cambium cells with repressed expression of the genes related to cell dividing activity. PtrCLE20 peptide also showed a repression effect on the root growth of Populus and Arabidopsis, likely through inhibiting meristematic cell dividing activity. Together, the results suggest that PtrCLE20 peptide, produced from developing xylem cells, plays a role in regulating lateral growth by repression of cambium activity in trees.
Sparse Kernel Canonical Correlation Analysis via $\ell_1$-regularization

Canonical correlation analysis (CCA) is a multivariate statistical technique for finding the linear relationship between two sets of variables. The kernel generalization of CCA named kernel CCA has been proposed to find nonlinear relations between datasets. Despite their wide usage, they have one common limitation that is the lack of sparsity in their solution. In this paper, we consider sparse kernel CCA and propose a novel sparse kernel CCA algorithm (SKCCA). Our algorithm is based on a relationship between kernel CCA and least squares. Sparsity of the dual transformations is introduced by penalizing the $\ell_{1}$-norm of dual vectors. Experiments demonstrate that our algorithm not only performs well in computing sparse dual transformations but also can alleviate the over-fitting problem of kernel CCA.
Reducing the impact of condensed tannins in a diet based on carob pulp using two levels of polyethylene glycol: lamb growth, digestion and meat quality

Fourteen male Comisana lambs were divided into two groups of seven at age 45 days and were fed a diet containing 56% of dried carob pulp (as fed basis). One group (P10) received a supple- ment of 10 g of polyethylene glycol (PEG) for each kg of diet, while the second group (P40) received a supplement of 40 g of PEG for each kg of diet. Both diets were ground and supplied ad libitum. The experimental diet contained 2.1% of condensed tannins (CT) on a dry matter basis. The lambs fed the P40 diet had higher average daily gain than the P10 lambs (P < 0.05) and obtained higher live weights at slaughter (P = 0.08) although the dry matter intake was not different between the treatments. The increased level of PEG (P40 vs. P10 lambs) increased dry matter digestibility (P = 0.07) and nitrogen (N) and neutral detergent fibre (NDF) digestibility (P < 0.01). The carcasses from the P40 lambs were heavier and fattier than those from the P10 lambs (P < 0.05). Meat (l. dorsi muscle) from the P10 lambs showed higher (P < 0.05) values of lightness (L*) compared to the P40 lambs. No differences in eating quality were registered among the groups. These results indicate that in a diet based on carob pulp (56%), 10 g of PEG per kg of diet are not sufficient to eliminate the effects of CT. carob pulp / meat quality / polyethylene glycol / sheep / tannins
Evaluating Enterprise Risk in a Complex Environment

This paper examines the relationship between operational risk management and knowledge learning process, with an emphasis on establishing the importance of statistical and mathematical approach on organizational capability to forecast, mitigate and control uncertain and vulnerable situations. Knowledge accumulation reduces critical situations unpredictability and improves organizational capability to face uncertain and potentially harmful events. We retain mathematical and statistical knowledge is organizational key factor in risk measuring and management process. Statistical creativity contributes to make quicker the innovation process of organization improves exploration capacity to forecast critical events and increases problem solving capacity, adaptation ability and learning process of organization. We show some important features of statistical approach. First, it makes clear strategic importance of risk culture within every level of organization; quantitative analysis support the emergence of latent troubles and make evident vulnerability of organization. Second, innovative tools allow to improve risk management and organizational capability to measure total risk exposition and to define a more adequate forecasting and corrective strategy. Finally, it’s not so easy to distinguish between measurable risk and unmeasurable uncertainty, it depends on quantity and quality of available knowledge. Difficulty predictable extreme events can bring out crisis and vulnerable situations. Every innovative approach which increases knowledge accumulation and improves forecasting process should be considered.
GUIDELINES FOR COPD AND NON-PHARMACOLOGICAL INTERVENTIONS

Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death. Prevalence rates are related to tobacco smoking and indoor air pollution, and are expected to rise as smoking rates continue to increase among women and in developing countries. By 2030, COPD is expected to represent the third leading cause of death. Caring for patients with advanced disease who experience frequent exacerbations places a significant burden on health care resources. Evidence on the natural history of COPD demonstrates early institution of long acting bronchodilator therapy slows the rate of lung function decline and reduces frequency of exacerbations that can lead to further functional decline. The goals of therapy are symptom control, reduce exacerbations, and maintain quality of life. Smoking cessation, pharmacotherapy with long acting bronchodilators, inhaled corticosteroids, pulmonary rehabilitation, and palliative care are important components. This review highlights current guidelines and management strategies for COPD.
The β-agonist lung injury trial (BALTI) : A randomized placebo-controlled clinical trial

Rationale: Experimental data suggest that manipulation of alveolar fluid clearance with β-agonists can accelerate the resolution of alveolar edema and improve survival.Objective: To determine if a sustained infusion of intravenous salbutamol (albuterol) would accelerate the resolution of alveolar edema in adult patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Methods: This was a single-center, double-blind, randomized controlled trial. Patients with ALI/ARDS were randomized to treatment with intravenous salbutamol (15 μg kg−1 h−1) or placebo for 7 d. The primary endpoint was extravascular lung water measured by thermodilution (PiCCO) at Day 7.Measurements and Main Results: Sixty-six patients were screened; of these, 40 met the inclusion criteria and were enrolled during 2001–2003. Patients in the salbutamol group had significantly lower lung water at Day 7 than the placebo group (9.2 ± 6 vs. 13.2 ± 3 ml kg−1; 95% confidence interval difference, 0.2–8.3 ml kg−1; p = 0.038.
Impact of Sugarcane Bagasse Ash as an Amendment on the Physical Properties, Nutrient Content and Seedling Growth of a Certified Organic Greenhouse Growing Media

Sugarcane bagasse is the fibrous material remaining after removing the sucrose, water, and other impurities (filter mud) from the millable sugarcane. Louisiana sugarcane mills use a portion of the sugarcane bagasse to produce steam power to run equipment within the mill and/or as a boiler fuel for the clarification, evaporation, and crystallization processes. Sugarcane bagasse ash (SBA) is a by-product of the thermal conversion of the sugarcane bagasse. The purpose of this research was to investigate the use of SBA as an amendment to soilless planting media for the production of vegetable seedlings. The SBA was combined by volume with a commercial certified organic soilless growing media into 5 combinations (0%:100%, 25%:75%, 50%:50%, 75%:25%, and 100%:0%, SBA and growing media, respectively). Bean (Phaseolus vulgaris L.) var. ‘Bowie’ and Chinese kale (Brassica alboglabra) var. ‘South Sea’ were planted in each of the 5 different planting mixtures. As the percentage of SBA increased from 0% to 100%, the bulk densities increased, 0.118 to 0.712 g/cm3, while the porosity, water saturation percentage, and water at field capacity decreased. Increasing the SBA percentage significantly impacted total exchange capacity, pH, organic matter, estimated nitrogen release, and all other nutrients measured, except for sodium. The research indicates that the addition of SBA can enhance bean and Chinese kale seedling growth depending on the percentage of the ash added to the growth media. Bean and Chinese kale harvest parameters typically peaked at 25% SBA, and then decreased with increasing SBA %. Adding 25% SBA did benefit the seedling growth by providing additional nutrients for seedling growth, while reducing the cost of production by supplementing the more expensive greenhouse media by a readily available by-product of the sugarcane industry. Increasing the SBA % to 50% or greater is not recommend. Additional research is needed to determine the percentage above 25% and below 50% SBA that would still benefit seedling plant growth.
Supplementary Information for Correlated protein conformational states and membrane dynamics during attack by pore forming toxins

Ilanila I.P, Ramesh Cheerla, K.Ganapathy Ayappa and Jaydeep K. Basu 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
Platform Thinking Strategic principles for orchestrating innovation ecosystems in the digital economy

I den digitala ekonomin agerar bolag i en allt med sammankopplad miljo, nagot som vi i den har studien kallar for att innovationsekosystem. For att blir framgangsrik i detta nya affarslandskap maste valetablerade bolag anamma nya innovationsstrategier. Vi foreslar har att dessa bolag bor anta ett plattformstankande for att orkestrera sitt innovationsekosystem. Till plattformstankande raknas de strategier som anvands utav valetablerade bolag for att exponera sin karntjanst eller karnprodukt for externa innovatorer i innovationsekosystemet. Vid en sadan exponering ser bolaget sin produkt eller tjanst som en plattform for innovation och deltagare i innovationsekosystemet kan gemensamt skapa ett storre varde an det varde som nagon av deltagarna skulle kunna skapa enskilt. Vi har anvant oss av en jamforande fallstudie for att undersoka vilka formagor som valetablerade foretag behover utveckla for att kunna anvanda sig av en plattform i ett innovationsekosystem. Vara resultat indikerar att valetablerade foretag maste utveckla fyra formagor: formagan att dela resurser utan att specificera innovationen pa forhand; formagan att fanga varde ifran flera olika intaktsstrommar; formagan att skydda vardet som skapats genom att skapa goda relationer; och formagan att skapa generativa strukturer. Den teoretiska konceptualiseringen av plattformstankande ar denna studies originella bidrag till plattforms- och ekosystemslitteraturen. Denna studie bidrar aven med ett praktiskt varde i form av djupare insikter kring de formagor som valetablerade foretag maste utveckla for att unyttja ett innovationsekosystem och lyckas i den digitala ekonomin.
Proactive Monitoring of Adalimumab Trough Concentration Associated With Increased Clinical Remission in Children with Crohn's Disease Compared with Reactive Monitoring.

BACKGROUND & AIMS Proactive monitoring of drug trough concentrations and antibodies against drugs might help determine whether patients are likely to respond to treatment and increase efficacy. We investigated whether proactive drug monitoring is associated with higher rates of clinical remission in pediatric patients with Crohn's disease (CD). METHODS We performed a non-blinded, randomized, controlled trial of 78 children with CD (6-18 years old; 29% female; mean age, 14.3±2.6 years) who had not received prior treatment with a biologic agent but had responded to adalimumab induction therapy, under scheduled monitoring of clinical and biologic measures (based on clinical factors and levels of C-reactive protein and fecal calprotectin), at pediatric gastroenterology units in Israel from July 2015 through December 2018. The patients were randomly assigned to groups that received proactive monitoring (trough concentrations measured at weeks 4 and 8 and then every 8 weeks until week 72, n=38) or reactive monitoring (physicians were informed of trough concentrations after loss of response, n=40). In both groups, doses and intervals of adalimumab were adjusted to achieve trough concentrations of 5 μgr/ml. The primary endpoint was sustained corticosteroid-free clinical remission at all visits (week 8 through week 72). RESULTS The primary endpoint was achieved by 31 children (82%) in the proactive group and 19 children (48%) in the reactive group (P=.002). Sixteen patients in the proactive monitoring group (42%) achieved a composite outcome of sustained corticosteroid-free remission, C-reactive protein ≤0.5mg/dL, and level of fecal calprotectin ≤150 μgr/gr compared with 5 patients in the reactive monitoring group (12%) (P=.003). By week 72 of treatment, 33 patients in the proactive monitoring group had received adalimumab intensification (87%) compared with 24 patients in the reactive monitoring group (60%) (P=.001). CONCLUSIONS In a randomized controlled trial of pediatric patients with CD, we found that proactive monitoring of adalimumab trough concentrations and adjustment of doses and intervals resulted in significantly higher rates corticosteroid-free clinical remission than reactive monitoring (measuring trough concentration after loss of response). Clinicaltrials.gov no: NCT02256462.
Culturally Sensitive OCD Research: Lessons from the U.S.-Mexico Border

Abstract This paper explores culturally-related concerns that arose during a multi-year study of obsessive-compulsive disorder (OCD) along the U.S.-Mexico border and describes adaptations made to better connect the research process to study participants. The purpose of this exploration is two-fold: (1) to offer suggestions for culturally sensitive borderland mental health research; and (2) to enhance dialog focused on culture, mental health research and the U.S.-Mexico border. Systematic coding of the written record of weekly research team meetings identified six recurring cultural concerns: emotionally charged and poorly understood terminology; differing meanings of ethnicity and acculturation; quality of life—regional variation and uncertainty; overlap of research and care; hopeful but hesitant; and fatalism. We conclude that diligence in the initial planning phase of a study is only part of the challenge in doing culturally sensitive research. Equally important is an ongoing process of evaluation to make explicit cultural concerns that arise during research, as well as a readiness to implement culturally sensitive research adaptations.
A reversible autophagy inhibitor blocks autophagosome–lysosome fusion by preventing Stx17 loading onto autophagosomes

Autophagy is an evolutionarily conserved intracellular lysosomal degradation pathway. It is a multistep process involving de novo formation of double membrane autophagosomes that capture cytosolic constituents (cargo) and eventually fuse with lysosomes wherein the cargo gets degraded and resulting simpler biomolecules get recycled. In addition to their autophagy function, several of the autophagy-related proteins work at the interface of other vesicular trafficking pathways. Hence, development of specific autophagy modulators that do not perturb general endo-lysosomal traffic possesses unique challenges. In this article, we report a novel small molecule EACC that inhibits autophagic flux by blocking autophagosome–lysosome fusion. Strikingly, unlike other late stage inhibitors, EACC does not have any effect on lysosomal properties or on endocytosis-mediated degradation of EGF receptor. EACC affects the translocation of SNAREs Stx17 and SNAP29 on autophagosomes without impeding the completion of autophagosomes. EACC treatment also reduces the interaction of Stx17 with the HOPS subunit VPS33A and the cognate lysosomal R-SNARE VAMP8. Interestingly, this effect of EACC although quite robust is reversible and hence EACC can be used as a tool to study autophagosomal SNARE trafficking. Our results put forward a novel method to block autophagic flux by impeding the action of the autophagosomal SNAREs.
College Students with Disabilities: The Relationship Between Student Characteristics, the Academic Environment, and Performance

Increasing numbers of individuals with disabilities are pursuing postsecondary education and training to assist them in achieving satisfying careers and sustainable earnings. Unfortunately, students with disabilities face numerous challenges leading to less than desirable college completion outcomes, with lower rates than their peers without disabilities. As a result of this disparity, there is a growing interest in the factors predicting academic success for students with disabilities. The purpose of this study was to examine modifiable factors (i.e., peer support, disability services, faculty teaching, campus climate, and self-advocacy) as potential predictors of higher academic performance for college students with disabilities. Three hundred and twenty-five students with disabilities from three large universities completed an online survey and participated in this study. Findings indicated that only one modifiable factor: self-advocacy, predicts higher grade point average. Implications for secondary and postsecondary professionals are discussed.