CRISPR/Cas9 systems are a versatile tool for genome editing due to the highly efficient targeting of DNA sequences complementary their RNA guide strands. However, it has been shown that RNA-guided Cas9 nuclease cleaves genomic containing mismatches strand. A better understanding specificity is needed minimize off-target cleavage in large mammalian genomes. Here we show sites could be cleaved by when contain insertions (‘DNA bulge’) or deletions (‘RNA compared strand, and nickases used paired...

Genome editing with engineered nucleases has recently emerged as an approach to correct genetic mutations by enhancing homologous recombination a DNA repair template. However, many diseases, such Duchenne muscular dystrophy (DMD), can be treated simply correcting disrupted reading frame. We show that genome transcription activator-like effector (TALENs), without template, efficiently the frame and restore expression of functional dystrophin protein is mutated in DMD. TALENs were mediate...

Duchenne muscular dystrophy (DMD) is caused by genetic mutations that result in the absence of dystrophin protein expression. Oligonucleotide-induced exon skipping can restore reading frame and production. However, this requires continuous drug administration may not generate complete targeted exon. In study, we apply genome editing with zinc finger nucleases (ZFNs) to permanently remove essential splicing sequences 51 gene thereby exclude from resulting transcript. This approach ~13% DMD...

Targeted gene addition to mammalian genomes is central biotechnology, basic research and therapy. For example, targeting the ROSA26 locus by homologous recombination in embryonic stem cells commonly used for mouse transgenesis achieve ubiquitous persistent transgene expression. However, conventional methods are not readily adaptable other cell types. The emerging zinc finger nuclease (ZFN) technology facilitates diverse species types, but an optimal strategy engineering highly active ZFNs...

This article summarizes the benefits and limitations of various approaches anterior cruciate ligament (ACL) rehabilitation, more specifically a conservative or traditional rehabilitation approach versus accelerated approach. The model is considered one with return to sport at 9 months later time-based criteria, an defined as goal by 6 months. Although there are some similarities between 2 types key differences exist will be highlighted. Additionally, we discuss criteria-based return-to-sport...

While dissemination and implementation (D&I) science has grown rapidly, there is an ongoing need to understand how build sustain capacity in individuals institutions conducting research. There are three inter-related domains for building: people, settings, activities. Since 2008, Washington University St. Louis dedicated significant attention resources toward building D&I research capacity. This paper describes our process, challenges, lessons with the goal of informing others who may have...

The use of big data in sport and management research is increasing popularity. Prior generally includes one the many characteristics data, such as volume or velocity. present study presents a multidimensional lens by considering sentiment analysis. Specifically focusing on phenomenon tanking, purposeful underperformance competitions, considers impact that consumers’ regarding tanking has game attendance National Basketball Association. Collecting social media posts for each Association team,...

As targeted treatments for amyloid transthyretin cardiomyopathy (ATTR-CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter-defibrillator (ICD) utilization, and their impact on survival.This is a retrospective cohort study 130 patients with ATTR-CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 September 2020. VAs were defined as nonsustained or sustained tachycardia fibrillation.Of patients, 42...

Sport teams historically have been reluctant to change ticket prices during the season. Recently, however, numerous sport organizations implemented variable pricing in an effort maximize revenues. In Major League Baseball results price increases or decreases depending on factors such as quality of opponent, day week, month year, and for special events opening day, Memorial Day, Independence Day. Using censored regression elasticity analysis, this article demonstrates that would yielded...

The pre-operative differentiation between enchondroma, low-grade chondrosarcoma and high-grade remains a diagnostic challenge. We reviewed the accuracy safety of radiological grading cartilaginous tumours through assessment of, first, post-operative histological agreement, second rate recurrence in lesions confirmed as on histology. performed retrospective review major long bone managed by curettage low grade 2001 2012. A total 53 patients with mean age 47.6 years (8 to 71) were included....

Abstract CRISPR/Cas9 systems have been used in a wide variety of biological studies; however, the large size presents challenges packaging it within adeno-associated viruses (AAVs) for clinical applications. We identified two-cassette system expressing pieces S. pyogenes Cas9 (SpCas9) protein which splice together cellula to form functional capable site-specific DNA cleavage. With specific CRISPR guide strands, we demonstrated efficacy this cleaving HBB and CCR5 genes human HEK-293T cells as...

Effective leadership for organizational change is critical to the implementation of evidence-based practices (EBPs). As leaders in behavioral health organizations often are promoted from within agency their long-standing, effective work as counselors, they may lack formal training leadership, management, or practice change. This study assesses a novel designed promote skills and successful specific EBP implementation. We conducted pre-post outcome evaluation Training Implementation Practice...

Previous research on spectator attendance has shown that there is a "honeymoon effect" for new facilities in Major League Baseball. Little research, however, been conducted examining the relationship between facility age and throughout life span of Baseball facilities. In this study, social psychology literature covering marital satisfaction cycle was used as theoretical framework an attempt to explain potentially similar An economic demand model created examine seasonal MLB from 1962 2001...

Astrocytomas are classified as either fibrillary or pilocytic on the basis of their histologic appearance. The imaging features astrocytoma correlate closely with tumor's clinical aggressiveness and are, therefore, useful in predicting prognosis. Correlation between astrocytoma, however, is not well established. Accordingly, we compared initial MR CT appearances lesion tumor seen clinically to determine if a correlation exists.We retrospectively evaluated images scans 32 consecutive patients...