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News Article | February 15, 2017
Site: www.prweb.com

Two-time National Basketball League (NBA) Most Valuable Player (MVP) Steph Curry will be a featured speaker at Liberty University Convocation on March 1, as part of a Kick’n It for Africa Humanitarian Partnership. Curry is considered by many basketball analysts to be the best shooter in the history of the game — he holds the record for most three-pointers made in a single NBA game (13 on Nov. 7, 2016) and broke the NBA record for most three-pointers made in a regular season three times (272 in 2012-13, 286 in 2014-15, 402 in 2015-16). He won an NBA championship with the Golden State Warriors in 2015. Curry was awarded the NBA MVP in back-to-back seasons, last year becoming the first player in league history to be selected for the honor by a unanimous vote. Kick’n It is a lifestyle brand founded by Liberty alumnus Chris “COSeezy” Strachan that utilizes pop culture and sneaker fashion to empower community service efforts. Strachan’s relationship with Curry — who is on Kick’n It’s advisory board — was instrumental in bringing the NBA star to Liberty. On March 1, Kick’n It will team up with another initiative, started by Liberty graduate student Emmanuel Ntibonera, a native of the Democratic Republic of the Congo (DRC). Ntibonera collects tennis shoes to send to less fortunate individuals in his home country. Liberty is asking students to bring a pair of shoes to donate to the cause on March 1. Additionally, Curry’s sponsor, Under Armour, will donate 1,000 pairs of children’s shoes. Liberty will deliver the shoes as part of a service trip to the DRC this summer. While Curry has not spoken at Convocation before, his wife, Food Network celebrity chef Ayesha Curry, was a featured guest last November. Curry’s younger brother, Seth Curry — currently of the NBA’s Dallas Mavericks — played his first collegiate season at Liberty, where he led all freshmen nationally in points per game and broke the Big South Conference single-season scoring record for a freshman. Convocation, held three times a week, is the world’s largest weekly gathering of Christian students. It provides a unique platform for Liberty students to hear from an array of educational and inspirational speakers. Convocation begins at 10:30 a.m. and can be viewed live at Liberty.edu/Watch. About Liberty University Liberty University, founded in 1971, is the largest private, nonprofit university in the nation, the largest university in Virginia, and the largest Christian university in the world. Located near the Blue Ridge Mountains on more than 7,000 acres in Lynchburg, Va., Liberty offers more than 500 unique programs of study from the associate to the doctoral level. More than 250 programs are offered online. Liberty’s mission is to train Champions for Christ with the values, knowledge, and skills essential for impacting tomorrow’s world.


News Article | February 15, 2017
Site: www.prweb.com

The 2017 Southeast Biking Symposium, being held March 23-25, 2017 at The Beach House on Hilton Head Island, has recently announced two guests who will serve as the conference’s Inspirational Keynote Speakers. Christian Vande Velde is a world-renowned member of the cycling community, famed for his fourth place finish in the Tour de France, his work as a broadcast analyst for NBC Sports and for his very public choice to come clean about his own struggles with doping. Now retired from the sport, Vande Velde has rekindled his love of biking among the picturesque Blue Ridge foothills of his adopted hometown of Greenville, South Carolina. Vande Velde will share his unique perspective on biking in the southeast, both as a pro and as a recreational cyclist, and talk about why he chose the Southeast to live, work and play, during this year’s Southeast Biking Symposium. Ashley Trexler is a freelance writer and inbound marketing specialist based in Hilton Head Island, South Carolina. Founder of the award-winning website LiesAboutParenting.com, her freelance writing and blog have seen millions of thumbs up. Published in print, online, and on-air, she contributes to a variety of publications, including The Washington Post and The Huffington Post. Trexler will speak on empowering parents to explore the world through biking. More than a series of seminars, The 2017 Southeast Biking Symposium Hilton Head Island will give participants the chance to build on our region’s rich bicycling tradition together, whether it be for active cyclists, seasoned riders or recreational biking. Symposium attendees will participate in, and take home, current and emerging trends for real-world implementation to drive cycling development throughout the southeast with topics focused on tourism, economic development and safety/infrastructure. Symposium registration will open next week; Visit hiltonheadisland.org/southeastbike for more information and hotel room block reservations. The Southeast Biking Symposium is presented by the Hilton Head Island Visitor & Convention Bureau with additional sponsorship from The Town of Hilton Head Island, Coligny Plaza, Toole Design Group, Palmetto Dunes Property Owners Association, The Hilton Head Island Bike Advisory Committee, Hilton Head Bicycle Company, ALTA Planning + Design and Kickin’ Asphalt Bike Club. Community partners include The Hilton Head Island Recreation Association and Coastal Discovery Museum. In cooperation with Palmetto Cycling Coalition and Georgia Bikes! The host hotel is The Beach House, an oceanfront resort in the Coligny district.


The physiological Src proto-oncogene is a protein-tyrosine kinase that plays key roles in cell growth, division, migration, and survival signaling pathways. From the N- to C-terminus, Src contains a unique domain, an SH3 domain, an SH2 domain, a protein-tyrosine kinase domain, and a regulatory tail. The chief phosphorylation sites of human Src include an activating pTyr419 that results from phosphorylation in the kinase domain by an adjacent Src molecule and an inhibitory pTyr530 in the regulatory tail that results from phosphorylation by C-terminal Src kinase (Csk) or Chk (Csk homologous kinase). The oncogenic Rous sarcoma viral protein lacks the equivalent of Tyr530 and is constitutively activated. Inactive Src is stabilized by SH2 and SH3 domains on the rear of the kinase domain where they form an immobilizing and inhibitory clamp. Protein kinases including Src contain hydrophobic regulatory and catalytic spines and collateral shell residues that are required to assemble the active enzyme. In the inactive enzyme, the regulatory spine contains a kink or a discontinuity with a structure that is incompatible with catalysis. The conversion of inactive to active Src is accompanied by electrostatic exchanges involving the breaking and making of distinct sets of kinase domain salt bridges and hydrogen bonds. Src-catalyzed protein phosphorylation requires the participation of two Mg2+ ions. Although nearly all protein kinases possess a common K/E/D/D signature, each enzyme exhibits its unique variations of the protein-kinase reaction template. Bosutinib, dasatinib, and ponatinib are Src/multikinase inhibitors that are approved by the FDA for the treatment of chronic myelogenous leukemia and vandetanib is approved for the treatment of medullary thyroid cancer. The Src and BCR-Abl inhibitors saracatinib and AZD0424, along with the previous four drugs, are in clinical trials for a variety of solid tumors including breast and lung cancers. Both ATP and targeted therapeutic Src protein kinase inhibitors such as dasatinib and ponatinib make hydrophobic contacts with catalytic spine residues and form hydrogen bonds with hinge residues connecting the small and large kinase lobes. ©2015 Elsevier Ltd. All rights reserved.


Groh G.I.,Blue Ridge | Groh G.M.,Blue Ridge
Journal of Shoulder and Elbow Surgery | Year: 2014

Background: Reverse shoulder arthroplasty (RSA) has ushered a new era in shoulder surgery. However, the results of RSA also described the complication rates associated with the procedure as inordinate and a learning curve associated with the incidence of complications. Methods: The records of 112 patients who underwent 114 RSA procedures by the senior author (G.I.G.) were reviewed for complications related to a RSA. Of these, 93 RSA procedures were the primary treatment for the shoulder, and 21 were revisions. Results: The total complication rate for the entire group was 7%. Complications included 3 periprosthetic fractures, 3 hematomas, 1 acromion fracture, and 1 deep infection. The complication rate was 19% in the revision RSA group and 4.3% in the primary RSA group (P ≤ .02). Complication rates in the initial RSA patients in this series did not differ from the final procedures in this series (P = .96). The total reoperation rate was 5.3%, and was 19% in the revision RSA group vs 2.2% in the primary RSA group (P ≤ .02). Conclusion: Complications and reoperations associated with a RSA, although significant, occurred at much lower rate than in previous reports. This series demonstrates a significant difference in complication rates and reoperation rates between primary and revision RSA. Revision RSA complications and reoperations were far more common than in primary RSA procedures. No evidence of a learning curve related to surgical experience was demonstrated in this series. © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees.


Roskoski R.,Blue Ridge
Pharmacological Research | Year: 2014

The human epidermal growth factor receptor (EGFR) family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). These receptors consist of a glycosylated extracellular domain, a single hydrophobic transmembrane segment, and an intracellular portion with a juxtamembrane segment, a protein kinase domain, and a carboxyterminal tail. Seven ligands bind to EGFR including epidermal growth factor and transforming growth factor α, none bind to ErbB2, two bind to ErbB3, and seven ligands bind to ErbB4. The ErbB proteins function as homo and heterodimers. The heterodimer consisting of ErbB2, which lacks a ligand, and ErbB3, which is kinase impaired, is surprisingly the most robust signaling complex of the ErbB family. Growth factor binding to EGFR induces a large conformational change in the extracellular domain, which leads to the exposure of a dimerization arm in domain II of the extracellular segment. Two ligand-EGFR complexes unite to form a back-to-back dimer in which the ligands are on opposite sides of the aggregate. Following ligand binding, EGFR intracellular kinase domains form an asymmetric homodimer that resembles the heterodimer formed by cyclin and cyclin-dependent kinase. The carboxyterminal lobe of the activator kinase of the dimer interacts with the amino-terminal lobe of the receiver kinase thereby leading to its allosteric stimulation. Downstream ErbB signaling modules include the phosphatidylinositol 3-kinase/Akt (PKB) pathway, the Ras/Raf/MEK/ERK1/2 pathway, and the phospholipase C (PLCγ) pathway. Several malignancies are associated with the mutation or increased expression of members of the ErbB family including lung, breast, stomach, colorectal, head and neck, and pancreatic carcinomas and glioblastoma (a brain tumor). Gefitinib, erlotinib, and afatinib are orally effective protein-kinase targeted quinazoline derivatives that are used in the treatment of ERBB1-mutant lung cancer. Lapatinib is an orally effective quinazoline derivative used in the treatment of ErbB2-overexpressing breast cancer. Trastuzumab, pertuzumab, and ado-trastuzumab emtansine, which are given intravenously, are monoclonal antibodies that target the extracellular domain and are used for the treatment of ErbB2-positive breast cancer; ado-trastuzumab emtansine is an antibody-drug conjugate that delivers a cytotoxic drug to cells overexpressing ErbB2. Cetuximab and panitumumab are monoclonal antibodies that target ErbB1 and are used in the treatment of colorectal cancer. Cancers treated with these targeted drugs eventually become resistant to them. The role of combinations of targeted drugs or targeted drugs with cytotoxic therapies is being explored in an effort to prevent or delay drug resistance in the treatment of these malignancies.© 2013 Elsevier Ltd. All rights reserved.


Roskoski Jr. R.,Blue Ridge
Pharmacological Research | Year: 2013

Anaplastic lymphoma kinase was first described in 1994 as the NPM-ALK fusion protein that is expressed in the majority of anaplastic large-cell lymphomas. ALK is a receptor protein-tyrosine kinase that was more fully characterized in 1997. Physiological ALK participates in embryonic nervous system development, but its expression decreases after birth. ALK is a member of the insulin receptor superfamily and is most closely related to leukocyte tyrosine kinase (Ltk), which is a receptor protein-tyrosine kinase. Twenty different ALK-fusion proteins have been described that result from various chromosomal rearrangements, and they have been implicated in the pathogenesis of several diseases including anaplastic large-cell lymphoma, diffuse large B-cell lymphoma, and inflammatory myofibroblastic tumors. The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. The formation of dimers by the amino-terminal portion of the ALK fusion proteins results in the activation of the ALK protein kinase domain that plays a key role in the tumorigenic process. Downstream signaling from ALK fusion proteins involves the Ras/Raf/MEK/ERK1/2 cell proliferation module and the JAK/STAT cell survival pathway. Furthermore, nearly two dozen ALK activating mutations participate in the pathogenesis of childhood neuroblastomas along with ALK overexpression. The occurrence of oncogenic ALK, particularly in non-small cell lung cancer, has generated considerable interest and effort in developing ALK inhibitors. Currently, crizotinib has been approved by the US Food and Drug Administration for the treatment of ALK-positive non-small cell lung cancer along with an approved fluorescence in situ hybridization kit used for the diagnosis of the disease. The emergence of crizotinib drug resistance with a median occurrence at approximately 10 months after the initiation of therapy has stimulated the development of second-generation drugs for the treatment of non-small cell lung cancer and other disorders. About 28% of the cases of crizotinib resistance are related to nearly a dozen different mutations of ALK in the EML4-ALK fusion protein; the other cases of resistance are related to the upregulation of alternative signaling pathways or to undefined mechanisms. It is remarkable that the EML4-ALK fusion protein was discovered in 2007 and crizotinib was approved for the treatment of ALK-positive non-small cell lung cancer in 2011, which is a remarkably short timeframe in the overall scheme of drug discovery. © 2012 Elsevier Ltd.


Groh G.I.,Blue Ridge
Journal of Shoulder and Elbow Surgery | Year: 2010

Background: Aseptic loosening of glenoid components is a common problem associated with total shoulder arthroplasty and one cause for failure. A new cementless fluted glenoid component was developed and has shown excellent bony ingrowth in a canine model. Hypothesis: Clinical utilization of this cementless fluted pegged glenoid component in total shoulder arthroplasty would lower rates of radiolucent lines and aseptic loosening. Materials and methods: Between January 2005 and December 2007, 83 primary shoulder arthroplasties with a minimum of 2 years' follow-up were performed with the uncemented fluted pegged glenoid component. Radiographs and records were reviewed to determine stability and survival of the glenoid component. Results: All cementless fluted pegged glenoid components had survived at the most recent clinical follow-up. Radiographs showed no evidence of component loosening or radiolucent lines. Evidence of fingerlike projections of bone between the flanges of the implant was found in 24 cases (29%). Conclusions: A cementless fluted pegged glenoid component showed excellent initial clinical survival and integration. Further studies regarding continued durability of this component appear warranted. © 2010 Journal of Shoulder and Elbow Surgery Board of Trustees.


Roskoski Jr. R.,Blue Ridge
Pharmacological Research | Year: 2014

The epidermal growth factor receptor (EGFR) family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). These receptors consist of an extracellular domain, a single hydrophobic transmembrane segment, and an intracellular portion with a juxtamembrane segment, a protein kinase domain, and a carboxyterminal tail. The ErbB proteins function as homo and heterodimers. Growth factor binding to EGFR induces a large conformational change in the extracellular domain. Two ligand-EGFR complexes unite to form a back-to-back dimer in which the ligands are on opposite sides of the aggregate. Following ligand binding, EGFR intracellular kinase domains form an asymmetric dimer. The carboxyterminal lobe of the activator kinase of the dimer interacts with the amino-terminal lobe of the receiver kinase thereby leading to its allosteric stimulation. Several malignancies are associated with the mutation or increased expression of members of the ErbB family including lung, breast, stomach, colorectal, head and neck, and pancreatic carcinomas. Gefitinib, erlotinib, and afatinib are orally effective protein-kinase targeted quinazoline derivatives that are used in the treatment of ERBB1-mutant lung cancer and lapatinib is an orally effective quinazoline derivative used in the treatment of ErbB2-overexpressing breast cancer. Moreover, monoclonal antibodies that target the extracellular domain of ErbB2 are used for the treatment of ErbB2-positive breast cancer and monoclonal antibodies that target ErbB1 and are used for the treatment of colorectal cancer. Cancers treated with these targeted drugs eventually become resistant to them, and a current goal of research is to develop drugs that are effective against drug-resistant tumors. © 2014 Elsevier Ltd.


Coatings, coating compositions and coating suspensions that contain solar reflective and/or shielding components for use in coating substrates such as cellulosic fiberboard construction materials. The coatings may vary in color from pink to red or from yellow to orange depending on which colorant or solar reflective pigment is used or combinations of colorants and solar reflective pigments is used. Methods of making and using the coatings and coating compositions/suspensions are also provided.


Coatings, coating compositions and coating suspensions that contain solar reflective and/or shielding components for use in coating substrates such as cellulosic fiberboard construction materials. The coatings may vary in color from pink to red or from yellow to orange depending on which colorant or solar reflective pigment is used or combinations of colorants and solar reflective pigments is used. Methods of making and using the coatings and coating compositions/suspensions are also provided.

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