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https://www.readbyqxmd.com/read/28633897/discovery-and-optimization-of-3-4-aryl-heteroarylsulfonyl-piperazin-1-yl-6-piperidin-1-yl-pyridazines-as-novel-cns-penetrant-pan-muscarinic-antagonists
#1
Aaron M Bender, Rebecca L Weiner, Vincent B Luscombe, Sonia Ajmera, Hyekyung P Cho, Sichen Chang, Xiaoyan Zhan, Alice L Rodriguez, Colleen M Niswender, Darren W Engers, Thomas M Bridges, P Jeffrey Conn, Craig W Lindsley
This letter describes the synthesis and structure activity relationship (SAR) studies of structurally novel M4 antagonists, based on a 3-(4-aryl/heteroarylsulfonyl)piperazin-1-yl)-6-(piperidin-1-yl)pyridazine core, identified from a high-throughput screening campaign. A multi-dimensional optimization effort enhanced potency at human M4 (hM4 IC50s<200nM), with only moderate species differences noted, and with enantioselective inhibition. Moreover, CNS penetration proved attractive for this series (rat brain:plasma Kp=2...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28630018/the-modified-ulaanbaatar-procedure-reduced-complications-and-enhanced-cosmetic-outcome-for-the-most-severe-cases-of-hypospadias
#2
V R Jayanthi, C B Ching, D G DaJusta, D J McLeod, S A Alpert
INTRODUCTION/OBJECTIVE: Proximal hypospadias is one of the most challenging conditions that pediatric urologists have to deal with. Many procedures have been devised over the years, but nothing has been proven to be the best option. Although there have been some attempts at correcting severe hypospadias in one procedure, most have advocated a staged approach. The classic approach - laying penile skin or a graft within a split glans followed by glanuloplasty at the second stage - by definition requires two operations on the glans...
May 18, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28629090/low-temperature-direct-heterogeneous-bonding-of-polyether-ether-ketone-and-platinum
#3
Weixin Fu, Akitsu Shigetou, Shuichi Shoji, Jun Mizuno
Direct heterogeneous bonding between polyether ether ketone (PEEK) and Pt was realized at the temperatures lower than 150°C. In order to create sufficient bondability to diverse materials, the surface was modified by vacuum ultraviolet (VUV) irradiation, which formed hydrate bridges. For comparison, direct bonding between surfaces atomically cleaned via Ar fast atom bombardment (FAB) was conducted in a vacuum. The VUV irradiation was found to be effective for creating an ultrathin hydrate bridge layer from the residual water molecules in the chamber...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28628944/bistable-solid-state-fluorescence-switching-in-photoluminescent-infinitely-coordinated-polymer
#4
Jincheol Kim, Youngmin You, Seong-Jun Yoon, Jong H Kim, Boseok Kang, Sang Kyu Park, Dong Ryeol Whang, Jangwon Seo, Kilwon Cho, Soo Young Park
Photo-functional infinitely coordinated polymers (ICPs) consisting of the photochromic dithienylethene (DTE) and the luminescent bridging unit to give enhanced fluorescence in the solid state were synthesized. We could fabricate well-ordered micropatterns of these ICPs by a soft-lithographic method, which repeatedly showed high contrast on-off fluorescence switching.
June 19, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28628609/a-multidimensional-integration-analysis-reveals-potential-bridging-targets-in-the-process-of-colorectal-cancer-liver-metastasis
#5
Bo Gao, Tian Yu, Dongbo Xue, Boshi Sun, Qin Shao, Hani Choudhry, Victoria Marcus, Jiannis Ragoussis, Yuguo Zhang, Weihui Zhang, Zu-Hua Gao
Approximately 9% of cancer-related deaths are caused by colorectal cancer. Liver metastasis is a major factor for the high colorectal cancer mortality rate. However, the molecular mechanism underlying colorectal cancer liver metastasis remains unclear. Using a global and multidimensional integration approach, we studied sequencing data, protein-protein interactions, and regulation of transcription factor and non-coding RNAs in primary tumor samples and liver metastasis samples to unveil the potential bridging molecules and the regulators that functionally link different stages of colorectal cancer liver metastasis...
2017: PloS One
https://www.readbyqxmd.com/read/28627383/science-communication-at-scientific-societies
#6
REVIEW
Jeanne Braha
Scientific societies can play a key role in bridging the research and practice of scientists' engagement of public audiences. Societies are beginning to support translation of science communication research, connections between scientists and audiences, and the creation of opportunities for scientists to engage publics without extensive customization. This article suggests roles, strategies, and mechanisms for scientific societies to promote and enhance their member's engagement of public audiences.
June 13, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28627031/the-influence-of-oxygen-atoms-on-conformation-and-%C3%AF-%C3%AF-stacking-of-ladder-type-donor-based-polymers-and-their-photovoltaic-properties
#7
Tong Qin, Yue Zang, Wei-Yun Bai, Kai Yao, Yun-Xiang Xu
A novel ladder-type donor pyran-bridged indacenodithiophene (IDTP) is developed by introducing two oxygen atoms into indacenodithiophene unit. IDTP possesses a twisted backbone and leads to facially asymmetric arrangement of side chains, resulting in enhanced local π-π stacking of according polymer poly[(5,5,11,11-tetrakis(4-octylphenyl)-5,11-dihydrothieno[2',3':5,6]pyrano[3,4-g]thieno[3,2-c]isochromene)-alt-4,7-(5-fluoro-2,1,3-benzothiadiazole)] (PIDTP)-FBT, which shows extended absorption range. Moreover, oxygen atoms render deeper highest occupied molecular orbital (HOMO) levels of poly[indacenodithiophene-alt-4,7-(5-fluoro-2,1,3-benzothiadiazole)] (PIDTP)-FBT compared with PIDT-FBT, therefore bringing a higher open-circuit voltage (Voc )...
June 19, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/28625790/preprotein-conformational-dynamics-drive-bivalent-translocase-docking-and-secretion
#8
Marios Frantzeskos Sardis, Alexandra Tsirigotaki, Katerina Elias Chatzi, Athina George Portaliou, Giorgos Gouridis, Spyridoula Karamanou, Anastassios Economou
Most bacterial secretory proteins destined beyond the plasma membrane are secreted post-translationally by the Sec translocase. In the first step of translocation, preproteins are targeted for binding to their 2-site receptor SecA, the peripheral ATPase subunit of the translocase. We now reveal that secretory preproteins use a dual-key mechanism to bridge the signal peptide and mature domain receptor sites and cooperatively enhance their affinities. Docking of targeting-competent mature domains requires that their extensive disorder is finely tuned...
June 5, 2017: Structure
https://www.readbyqxmd.com/read/28622983/the-effect-of-a-comprehensive-care-transition-model-on-cost-and-utilization-for-medically-complex-children-with-cerebral-palsy
#9
Steven W Howard, Zidong Zhang, Paula Buchanan, Eric Armbrecht, Christine Williams, Geneva Wilson, Janna Hutchinson, Lindsey Pearson, Samantha Ellsworth, Caitlin M Byler, Travis Loux, Jing Wang, Steph Bernell, Nicholas Holekamp
INTRODUCTION: Our aim was to evaluate cost and acute care utilization related to an organized approach to care coordination and transitional care after major acute care hospitalization for children with medical complexities, including cerebral palsy. METHODS: A retrospective cohort of 32 patients from Ranken Jordan Pediatric Bridge Hospital (RJPBH) who received the Care Beyond the Bedside model was compared with 151 patients receiving standard care elsewhere across Missouri...
June 13, 2017: Journal of Pediatric Health Care
https://www.readbyqxmd.com/read/28622604/tissue-engineered-hypertrophic-chondrocyte-grafts-enhanced-long-bone-repair
#10
Jonathan Bernhard, James Ferguson, Bernhard Rieder, Patrick Heimel, Thomas Nau, Stefan Tangl, Heinz Redl, Gordana Vunjak-Novakovic
Bone has innate ability to regenerate following injury. However, large and complex fractures exceed bone's natural repair capacity and result in non-unions, requiring external intervention to facilitate regeneration. One potential treatment solution, tissue-engineered bone grafts, has been dominated by recapitulating intramembranous ossification (bone formation by osteoblasts), although most serious bone injuries heal by endochondral ossification (bone formation by remodeling of hypertrophic cartilaginous anlage)...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28616173/modeling-connectivity-to-identify-current-and-future-anthropogenic-barriers-to-movement-of-large-carnivores-a-case-study-in-the-american-southwest
#11
Meredith L McClure, Brett G Dickson, Kerry L Nicholson
This study sought to identify critical areas for puma (Puma concolor) movement across the state of Arizona in the American Southwest and to identify those most likely to be impacted by current and future human land uses, particularly expanding urban development and associated increases in traffic volume. Human populations in this region are expanding rapidly, with the potential for urban centers and busy roads to increasingly act as barriers to demographic and genetic connectivity of large-bodied, wide-ranging carnivores such as pumas, whose long-distance movements are likely to bring them into contact with human land uses and whose low tolerance both for and from humans may put them at risk unless opportunities for safe passage through or around human-modified landscapes are present...
June 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28613905/unexpected-effects-of-activator-molecules-polarity-on-the-electroreological-activity-of-titanium-dioxide-nanopowders
#12
Alexander Viktorovich Agafonov, Olga I Davydova, Anton S Krayev, Olga S Ivanova, Olga L Evdokimova, Tatiana V Gerasimova, Alexander E Baranchikov, Vladimir V Kozik, Vladimir K Ivanov
Titanium dioxide nanoparticles, obtained using the sol-gel method and modified with organic solvents such as acetone, acetonitrile, benzene, diethyl ether, dimethylsulfoxide, toluene and chloroform, were used as the filler of polydimethylsiloxane-based electrorheological fluids. The effect of electric field strength on the shear stress and yield stress of electrorheological fluids was investigated, as well as the spectra of their dielectric relaxation in the frequency range from 25 to 106 Hz. Modification of titanium dioxide by polar molecules was found to enhance the electrorheological effect, as compared with unmodified TiO2, in accordance with the widely accepted concept of polar molecule dominated electrorheological effect (PM-ER)...
June 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28613008/n-channel-organic-semiconductors-derived-from-air-stable-four-coordinate-boron-complexes-of-substituted-thienylthiazoles
#13
Reinhard Hecht, Juliane Kade, David Schmidt, Agnieszka Nowak-Król
Three acceptor-π-bridge-acceptor (A-π-A) molecules derived from 2-(3-boryl-2-thienyl)thiazole have been synthesized and thoroughly characterized. Incorporation of a B-N unit into thienylthiazole and attachment of suitable acceptor moieties allowed to obtain ambient-stable A-π-A molecules with low-lying LUMO levels. Their potential for applications in organic electronics was tested in vacuum-deposited organic thin film transistors (OTFT). The OTFT device based on boryl-thienylthiazole donor and 1,1-dicyanomethylene-3-indandione (DCIND) acceptor moieties showed an electron mobility of ~1...
June 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28610649/enhancing-resiliency-for-elderly-populations-shelter-in-place-planning-and-training-at-facilities-serving-elderly-populations-through-the-rhode-island-senior-resiliency-project
#14
Richard Smith, Michael Mozzer, Joseph Albanese, James Paturas, Julia Gold
Elderly populations are disproportionately affected by disasters. In part, this is true because for many older adults, special assistance is needed to mitigate the consequences of disasters on their health and wellbeing. In addition, many older adults may reside in diverse living complexes such as long-term care facilities, assisted living facilities and independent-living senior housing complexes. Planning for each type of facility is different and the unique features of these facilities must be considered to develop readiness to deal with disasters...
June 1, 2017: Journal of Business Continuity & Emergency Planning
https://www.readbyqxmd.com/read/28608618/bench-to-bedside-bridge-enhanced-anterior-cruciate-ligament-repair
#15
REVIEW
Gabriel S Perrone, Benedikt L Proffen, Ata M Kiapour, Jakob T Sieker, Braden C Fleming, Martha M Murray
Anterior cruciate ligament (ACL) injuries are one of the most well-known orthopaedic injuries and are treated with one of the most common orthopaedic procedures performed in the United States. This surgical procedure, ACL reconstruction, is successful at restoring the gross stability of the knee. However, the outcomes of ACL reconstruction can be limited by short and long term complications, including muscle weakness, graft rupture and premature osteoarthritis. Thus, new methods of treating this injury are being explored...
June 13, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28607559/bone-marrow-aspirate-concentrate-enhanced-marrow-stimulation-of-chondral-defects
#16
REVIEW
Henning Madry, Liang Gao, Hermann Eichler, Patrick Orth, Magali Cucchiarini
Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28603790/dual-layer-groupwise-registration-for-consistent-labeling-of-longitudinal-brain-images
#17
Minjeong Kim, Guorong Wu, Isrem Rekik, Dinggang Shen
The growing collection of longitudinal images for brain disease diagnosis necessitates the development of advanced longitudinal registration and anatomical labeling methods that can respect temporal consistency between images. However, the characteristics of such longitudinal images and how they lodge into the image manifold are often neglected in existing labeling methods. Indeed, most of them independently align atlases to each target time-point image for propagating the pre-defined atlas labels to the subject domain...
October 2016: Machine Learning in Medical Imaging
https://www.readbyqxmd.com/read/28599636/health-coaching-to-improve-self-management-and-quality-of-life-for-low-income-patients-with-chronic-obstructive-pulmonary-disease-copd-protocol-for-a-randomized-controlled-trial
#18
Beatrice Huang, Rachel Willard-Grace, Denise De Vore, Jessica Wolf, Chris Chirinos, Stephanie Tsao, Danielle Hessler, George Su, David H Thom
BACKGROUND: Chronic obstructive pulmonary disease (COPD) severely hinders quality of life for those affected and is costly to the health care system. Care gaps in areas such as pharmacotherapy, inhaler technique, and knowledge of disease are prevalent, particularly for vulnerable populations served by community clinics. Non-professionally licensed health coaches have been shown to be an effective and cost-efficient solution in bridging care gaps and facilitating self-management for patients with other chronic diseases, but no research to date has explored their efficacy in improving care for people living with COPD...
June 9, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28597004/increased-binding-of-apolipoproteins-a-i-and-e4-to-triglyceride-rich-lipoproteins-is-linked-to-induction-of-hypertriglyceridemia
#19
Irina N Gorshkova, David Atkinson
Hypertriglyceridemia (HTG) is an independent factor of atherosclerotic cardiovascular disease and a hallmark of many metabolic disorders. However, the molecular etiology of HTG is still largely unknown. In mice, severe HTG may be induced by expression of specific mutants of apolipoprotein (apo) A-I or wild type (WT) apoE4. Expression of a certain apoE4 mutant results in mild HTG, while expression of another apoE4 mutant or WT apoA-I results in normal plasma triglyceride (TG) levels. Biophysical studies of the apoA-I and apoE4 forms associated with HTG help better understand the molecular mechanisms of induction of HTG by these proteins...
2017: JSM Atheroscler
https://www.readbyqxmd.com/read/28595983/the-effects-of-structure-on-pre-mrna-processing-and-stability
#20
REVIEW
Rachel Soemedi, Kamil J Cygan, Christy Rhine, David T Glidden, Allison J Taggart, Chien-Ling Lin, Alger M Fredericks, William G Fairbrother
Pre-mRNA molecules can form a variety of structures, and both secondary and tertiary structures have important effects on processing, function and stability of these molecules. The prediction of RNA secondary structure is a challenging problem and various algorithms that use minimum free energy, maximum expected accuracy and comparative evolutionary based methods have been developed to predict secondary structures. However, these tools are not perfect, and this remains an active area of research. The secondary structure of pre-mRNA molecules can have an enhancing or inhibitory effect on pre-mRNA splicing...
June 5, 2017: Methods: a Companion to Methods in Enzymology
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