http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Connelly, Stephen,Mortenson, David E.,Choi, Sungwook,Wilson, Ian A.,Powers, Evan T.,Kelly, Jeffery W.,Johnson, Steven M. Pergamon Press 2017 Bioorganic & medicinal chemistry letters Vol.27 No.15
<P><B>Abstract</B></P> <P>Rate-limiting dissociation of the tetrameric protein transthyretin (TTR), followed by monomer misfolding and misassembly, appears to cause degenerative diseases in humans known as the transthyretin amyloidoses, based on human genetic, biochemical and pharmacologic evidence. Small molecules that bind to the generally unoccupied thyroxine binding pockets in the native TTR tetramer kinetically stabilize the tetramer, slowing subunit dissociation proportional to the extent that the molecules stabilize the native state over the dissociative transition state—thereby inhibiting amyloidogenesis. Herein, we use previously reported structure-activity relationship data to develop two semi-quantitative algorithms for identifying the structures of potent and selective transthyretin kinetic stabilizers/amyloidogenesis inhibitors. The viability of these prediction algorithms, in particular the more robust <I>in silico</I> docking model, is perhaps best validated by the clinical success of tafamidis, the first-in-class drug approved in Europe, Japan, South America, and elsewhere for treating transthyretin aggregation-associated familial amyloid polyneuropathy. Tafamidis is also being evaluated in a fully-enrolled placebo-controlled clinical trial for its efficacy against TTR cardiomyopathy. These prediction algorithms will be useful for identifying second generation TTR kinetic stabilizers, should these be needed to ameliorate the central nervous system or ophthalmologic pathology caused by TTR aggregation in organs not accessed by oral tafamidis administration.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
High-Rosmarinic Acid Spearmint Tea in the Management of Knee Osteoarthritis Symptoms
A. Erin Connelly,Amy J. Tucker,Hilary Tulk,Marisa Catapang,Lindsey Chapman,Natasha Sheikh,Svitlana Yurchenko,Ron Fletcher,Laima S. Kott,Alison M. Duncan,Amanda J. Wright 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.12
Individuals with medically diagnosed knee osteoarthritis (OA) participated in a randomized, double-blind study to investigate the effects of a high-rosmarinic acid (rosA) spearmint tea. Sixty-two participants were randomized by sex and screening pain score to consume tea brewed from a high-rosA spearmint variety or a commercially available spearmint twice daily for 16 weeks. Pain, quality of life (QoL), and physical function at baseline and week 16 were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short-Form 36-item Health Survey (SF-36), 6-minute walk test (6MWT), and stair climb test (SCT). Data from 46 participants (mean age = 60.7; BMI = 32.9 kg/m2) were analyzed. Pain score significantly decreased from week 0 to 16 for the high-rosA group but not for the control group and scores for stiffness and physical disability significantly decreased from week 0 to 16 for both groups. Increased QoL score on the bodily pain index in the SF-36 was observed at week 16 within the high-rosA group only, although no significant differences were observed between the groups. A nonsignificant improvement was observed in the 6MWT at week 16 in the high-rosA group only. There were no changes in the SCT for either group. Therefore, 16-week daily consumption of the highrosA and commercial spearmint teas significantly improved stiffness and physical disability scores in adults with knee OA, but only the high-rosA tea significantly decreased pain. Consumption of high-rosA tea warrants further consideration as a potential complementary therapy to reduce pain in OA. Clinical Trial Registration Number: NCT01380015.
Myung, Nojoon,Connelly, Stephen,Kim, Boyoung,Park, Sung Jean,Wilson, Ian A.,Kelly, Jeffery W.,Choi, Sungwook The Royal Society of Chemistry 2013 Chemical communications Vol.49 No.80
<P>We describe coumarin derivatives that are non-fluorescent in aqueous buffers and that very selectively bind to transthyretin (TTR) in complex biological environments potently inhibiting TTR amyloidogenesis while also exhibiting sensitive off–on fluorescent sensing of the properly folded quaternary structure of TTR.</P> <P>Graphic Abstract</P><P>Two coumarin derivatives obtained by structure-based design are potent transthyretin kinetic stabilizers (amyloid inhibitors) and sensitive fluorescent transthyretin folding sensors. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3cc44667k'> </P>
Nehama Lewis,Yaron Connelly,Gil Henkin,Max Leibovich,Adi Akavia 대한의료정보학회 2022 Healthcare Informatics Research Vol.28 No.2
Objectives: Healthcare organizations that maintain and process Electronic Medical Records are at risk of cyber-attacks,which can lead to breaches of confidentiality, financial harm, and possible interference with medical care. State-of-the-artmethods in cryptography have the potential to offer improved security of medical records; nonetheless, healthcare providersmay be reluctant to adopt and implement them. The objectives of this study were to assess current data management andsecurity procedures; to identify attitudes, knowledge, perceived norms, and self-efficacy regarding the adoption of advancedcryptographic techniques; and to offer guidelines that could help policy-makers and data security professionals work togetherto ensure that patient data are both secure and accessible. Methods: We conducted 12 in-depth semi-structured interviewswith managers and individuals in key cybersecurity positions within Israeli healthcare organizations. The interviews assessedperceptions of the feasibility and benefits of adopting advanced cryptographic techniques for enhancing data security. Qualitativedata analysis was performed using thematic network mapping. Results: Key data security personnel did not perceiveadvanced cybersecurity technologies to be a high priority for funding or adoption within their organizations. We identifiedthree major barriers to the adoption of advanced cryptographic technologies for information security: barriers associatedwith regulators; barriers associated with healthcare providers; and barriers associated with the vendors that develop cybersecuritysystems. Conclusions: We suggest guidelines that may enhance patient data security within the healthcare system andreduce the risk of future data breaches by facilitating cross-sectoral collaboration within the healthcare ecosystem.
Richard N. Ranson,Jennifer H. Connelly,Robert M. Santer,Alan H. D. Watson 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.4
In rats, ageing results in dysfunctional patterns of micturition and diminished sexual reflexes that may reflect degenerative changes within spinal circuitry. In both sexes the dorsal lateral nucleus and the spinal nucleus of the bulbospongiosus, which lie in the L5-S1 spinal segments, contain motor neurons that innervate perineal muscles, and the external anal and urethral sphincters. Neurons in the sacral parasympathetic nucleus of these segments provide autonomic control of the bladder, cervix and penis and other lower urinary tract structures. Interneurons in the dorsal gray commissure and dorsal horn have also been implicated in lower urinary tract function. This study investigates the cellular localisation of PG-21 androgen receptors, steroid receptor co-activator one (SRC-1) and the phosphorylated form of c-AMP response element binding protein (pCREB) within these spinal nuclei. These are components of signalling pathways that mediate cellular responses to steroid hormones and neurotrophins. Nuclear expression of PG-21 androgen receptors, SRC-1 and pCREB in young and aged rats was quantified using immunohistochemistry. There was a reduction in the number of spinal neurons expressing these molecules in the aged males while in aged females, SRC-1 and pCREB expression was largely unchanged. This suggests that the observed age-related changes may be linked to declining testosterone levels. Acute testosterone therapy restored expression of PG-21 androgen receptor in aged and orchidectomised male rats, however levels of re-expression varied within different nuclei suggesting a more prolonged period of hormone replacement may be required for full restoration.
( Hyung Won Kim ),( Tim Fukawa Connelly ) 한국수학교육학회 2015 수학교육 Vol.54 No.3
This study qualitatively investigates the nature of the challenges that a student who is highly successful in mathematics faces in learning college-level elementary statistics. The study draws on the constructs of eagerness, flexibility and willingness to characterize the necessary disposition for critical thinking that is essential in learning statistics. The case study is based on data collected through a survey assessment and a follow-up interview with a mathematics major enrolled in an elementary college statistics course at the time of the study. The qualitative analysis relies on the student`s verbal descriptions of the challenges he was experiencing in the course. The findings suggest that while his strong inclination towards inquisitive learning and strong understanding of mathematical concepts supported this student`s mathematics learning, the same characteristics might have been causing him difficulties in learning college-level elementary statistics