BSA
Montreal, Canada
Montreal, Canada

The British South Africa Company was established following the amalgamation of Cecil Rhodes' Central Search Association and the London-based Exploring Company Ltd which had originally competed to exploit the expected mineral wealth of Mashonaland but united because of common economic interests and to secure British government backing. The company received a Royal Charter in 1889 modelled on that of the British East India Company. Its first directors included the Duke of Abercorn, Rhodes himself and the South African financier Alfred Beit. Rhodes hoped BSAC would promote colonisation and economic exploitation across much of south-central Africa, as part of the "Scramble for Africa". However, his main focus was south of the Zambezi, in Mashonaland and the coastal areas to its east, from which he believed the Portuguese could be removed by payment or force, and in the Transvaal, which he hoped would return to British control.It has been suggested that Rhodes' ambition was to create a zone of British commercial and political influence from "Cape to Cairo", but this was far beyond the resources of any commercial company to achieve and would not have given investors the financial returns they expected. BSAC was created in the expectation that the gold fields of Mashonaland would provide funds for the development of other areas of Central Africa, including the mineral wealth of Katanga. When the expected wealth of Mashonaland did not materialise and Katanga was acquired by the Congo Free State, the company had little money left after building railways for significant development, particularly in areas north of the Zambezi. BSAC regarded its lands north of the Zambezi as territory to be held as cheaply as possible for future, rather than immediate, exploitation.As part of administering Southern Rhodesia until 1923 and Northern Rhodesia until 1924, BSAC formed what were originally paramilitary forces, but which later included more normal police functions. In addition to the administration of Southern and Northern Rhodesia, BSAC claimed extensive landholdings and mineral rights in both the Rhodesias and, although its land claims in Southern Rhodesia were nullified in 1918, its land rights in Northern Rhodesia and its mineral rights in Southern Rhodesia had to be bought out in 1924 and 1933 respectively, and its mineral rights in Northern Rhodesia lasted until 1964. BSAC also created the Rhodesian railway system and owned the railways there until 1947. Wikipedia.


Time filter

Source Type

News Article | April 26, 2017
Site: www.marketwired.com

SINGAPORE--(Marketwired - Apr 25, 2017) - As the world celebrates Earth Day, 23 bizhub Multi-Function Printers (MFP) models from Konica Minolta Business Solutions Asia (BSA) were awarded the Singapore Green Label, Singapore's most established eco-labelling scheme for industrial and commercial products. Awarded by the Singapore Environment Council, the label recognizes products with environmentally friendly attributes. To be awarded the Singapore Green Label in the category of 'Copying Machines, Printers, Fax Machines & Multifunctional Devices', a product must meet several production and operational standards, which include: Ms Jen Teo Pui Heng, Executive Director of the Singapore Environment Council, said: "By obtaining the Singapore Green Label certification for their products, Konica Minolta has demonstrated a clear commitment to protecting the environment. Konica Minolta will benefit from the growing number of companies, government agencies and individuals that look for eco-labels when making a purchasing decision. We congratulate Konica Minolta on their efforts to improve the environmental standards of their customers and stakeholders through their products." "It is our goal to ensure that our products make a positive impact on our customers and the environment through external and internal validation", said Jonathan Yeo, General Manager, Regional Headquarters, Konica Minolta BSA. "To that end, we are committed to expanding its portfolio of eco-friendly products, an initiative line with our Green Products global strategy." Last year, 60% of Konica Minolta's global sales comprised Green Products - the company's own eco certification system which aims to preserving biodiversity and supporting recycling. This was an increase from 57% in 2015. "As an organization that has been named to the Dow Jones Sustainability World Index for five years in a row, we want to continually increase the proportion of our solutions to reduce our environmental impact on the world and create a true workplace of the future", Mr Yeo continued. The line of bizhub MFP models awarded are:


LEADVILLE, Colo.--(BUSINESS WIRE)--Prazen Living Legend of Mining Award - The National Mining Hall of Fame and Museum’s Board of Directors is pleased to announce the 2017 Prazen Living Legend of Mining Award will be presented to the Boy Scouts of America (BSA) at the 30th Annual National Mining Hall of Fame Induction Banquet on September 23, 2017 in Denver, CO. Every year, the National Mining Hall of Fame and Museum (NMHFM) selects an individual or entity that has demonstrated ongoing, innovative work educating the public, policy makers, educators, or related institutions about the importance of the mineral and mining industry to our everyday lives. The awardee is selected from a pool of nominations reviewed by the National Mining Hall of Fame’s Prazen committee. The BSA has implemented a multi-faceted program that highlights the important role minerals play in our quality of life and national security. Through the launch and promotion of the Mining in Society Merit Badge program and other program initiatives, the BSA has substantially increased awareness of the role minerals play in our way of life, and has identified the conservation-minded means of extracting and processing minerals. The BSA has demonstrated a successful and continuing commitment to educate the public on the importance of the minerals industries. The Mining in Society merit badge was launched in February 2014 during the Society for Mining, Metallurgy and Exploration Annual Conference and Expo in Salt Lake City, UT. The badge has been well received, with more than 12,000 Scouts earning the badge by the end of 2016. The merit badge pamphlet is an excellent primer on mining. The pamphlet explains the key role that mined products play in our quality of life. The pamphlet is written and illustrated at a level that youth and the general public can understand and appreciate. The requirements that a Scout must complete to earn the badge help to build a lifelong understanding of how important minerals are to society. Further, the pamphlet identifies the multitude of career tracks offered in the mining industry. The Mining in Society merit badge has created an “engine” with the potential to reach nearly 1,000,000 Scouts in the U.S. Considering the “multiplier effect,” where families discuss endeavors of their children, and Scouts earning the badge interact with schoolmates and friends, the educational outreach of the Mining in Society Merit Badge is likely to be multiplied well beyond the number of those with a permanent means and channel to reach out to the public to educate and tell the story of mining and its necessity in the everyday life of all people. Frank McAllister, NMHFM Board of Directors Chairman, commented, “ The Mining in Society merit badge provides today’s youth with a glimpse into what makes their lives and their world so extraordinary. It provides an understanding that minerals and metals are key to everything we as humans do; a perspective that these natural endowments are life-essentials important to society.” The National Mining Hall of Fame and Museum is located in Leadville, CO. It is the only federally chartered mining hall of fame and museum in the United States and is the premier showcase of American mining, telling the story about mining, its people, and its importance to the American public. More information about the Prazen Living Legend of Mining Award, this year’s inductees into the National Mining Hall of Fame, and the Annual Induction Banquet to honor them can be found at www.MiningHallofFame.org.


For the first time in its 9-year history, The Quail Motorcycle Gathering took the show on the road with an appearance at Revival Cycles’ The Handbuilt Motorcycle Show. Guests of this annual festival in Austin, Texas were treated to a special preview of some of the bikes that will grace the lawn at Quail Lodge & Golf Club on Saturday, May 6, 2017. “For the past several years, we have enjoyed hosting Revival Cycles and some of their amazing work,” commented Gordon McCall, Director of Motorsports for The Peninsula Signature Events. “Aligning our brands by supporting each other's vision has been a natural fit, as we both are striving for motorcycling excellence. It was an honor to support their event and bring a piece of The Quail Motorcycle Gathering out to the folks in Austin. We’d like to thank Revival Cycles for hosting us, and we look forward to another great event in May.” With the help of longtime supporter Herb Harris, McCall was able to turn a small part of the show’s footprint into a scene reminiscent of sunny spring days on the lawn of Quail Lodge & Golf Club. Perched atop a patch of artificial grass were three Vincent Black Shadows and a BSA race bike, as well as a pair of rare Brough Superiors supplied by Revival Cycles. “The Quail Motorcycle Gathering exhibit was very well received and extremely popular with the crowds at this year’s Handbuilt Show,” added Revival Cycles / Handbuilt Show co-founder Alan Stulberg. “We wanted to further promote the desegmentation of the motorcycle show world, and we felt like Gordon’s display did that perfectly. Now we are gearing up to bring a few unique bikes with us to The Quail Motorcycle Gathering, including the world’s first custom Confederate Motorcycle.” Come experience an entire weekend filled with live entertainment, lifestyle vendors and more than 400 motorcycles on display, only at The Quail Motorcycle Gathering. Attendees can save $20 by purchasing discounted pre-sale tickets online at www.quaillodgetickets.com. Full-price tickets will also be available at the gate on the day of the event. Entry includes a gourmet barbecue lunch, parking, and gear valet service for those riding a motorcycle to the event. Learn more on the event website and follow the action on Facebook, Instagram and Twitter.


Le 22 septembre 2016, l'assemblée générale a autorisé le conseil d'administration de la Société à émettre 2 006 097 nouvelles actions (représentant 100% du capital émis et en circulation à ce moment) et exclure tout droit de préemption pour les actionnaires existants dans le cadre de cette émission pour une période de trois ans. Les nouvelles Actions liées au placement privé ont été émises par le Conseil d'Administration, avec l'approbation du Conseil de Surveillance, en vertu de cette délégation existante par l'assemblée générale. En outre, le Conseil de Surveillance a préalablement consenti à l'émission par le Conseil d'Administration d'un nombre supplémentaire d'Actions au besoin lors de l'exercice des BSA et de la conversion des ODIRNANE. Le placement privé de nouvelles Actions et Warrants n'est pas basé sur un prospectus approuvé par l'Autorité Néerlandaise pour les Marchés Financiers, l'AFM ou l'Autorité Française, l'AMF. Par ailleurs, Kreos Capital a signé un accord avec l’Investisseur dans lequel (i) celui-ci s’engage à (a) ne faire valoir aucun de ses droits en lien avec la Dette Kreos jusqu’au 30 novembre 20185 et (b) limiter ses ventes d’actions sur le marché jusqu’au 30 septembre 2017 (Kreos Capital (x) ne pourra pas vendre d’actions si la liquidité moyenne quotidienne de l’action de la Société est inférieure à 25 k€, (y) pourra vendre un montant maximum de 100 k€ d’actions par mois calendaire si la liquidité moyenne quotidienne de l’action de la Société est comprise entre 25 k€ et 75 k€, et (z) pourra vendre un montant maximum de 250 k€ d’actions par mois calendaire si la liquidité moyenne quotidienne de l’action de la Société est supérieure à 75 k€), et (ii) Kreos Capital donne une option d’achat à l’Investisseur sur la Dette Kreos au nominal. NOXXON Pharma N.V. est une société biopharmaceutique développant principalement des traitements contre le cancer. L'objectif de NOXXON est d'améliorer significativement l'efficacité des traitements anticancéreux, notamment les approches immuno-oncologiques (inhibiteurs de point de contrôle immunitaire) et les traitements actuels plus courants (chimiothérapie et radiothérapie). La plateforme de Spiegelmers de NOXXON a permis le développement d’un portefeuille exclusif de produits candidats au stade clinique, dont son candidat médicament anticancéreux phare, NOX-A12 qui est le sujet d’un collaboration en immuno-oncologie avec Merck & Co. Inc / MSD (NYSE:MRK) pour réaliser une étude clinique sur NOX-A12 associé au Keytruda® (pembrolizumab) dans le cancer du pancréas et le cancer colorectal. NOXXON est soutenu par des investisseurs internationaux de renom, dont TVM Capital, Sofinnova Partners, Edmond de Rothschild Investment Partners, DEWB, NGN et Seventure. Son siège social se situe à Amsterdam, aux Pays-Bas et ses bureaux à Berlin, en Allemagne. De plus amples informations peuvent être consultées sur www.noxxon.com. Ce communiqué contient des déclarations prospectives ou des termes se rapportant aux développements futurs ou futurs, ainsi que les négations de telles formulations ou termes, ou une terminologie similaire. Ces déclarations ne constituent pas des faits historiques. Ces déclarations comprennent des projections et des estimations ainsi que les hypothèses sur lesquelles celles-ci reposent, des déclarations portant sur des projets, des objectifs, des intentions et des attentes concernant des résultats financiers, des événements, des opérations, des services futurs, le développement de produits et leur potentiel ou les performances futures. La société ne prend aucun engagement de mettre à jour les informations et déclarations prospectives, qui ne représente que l'état des choses le jour de la publication. i. Concernant les tranches n°2 à n°6, plus de 2 mois se sont écoulés depuis le plus tard de (i) la date de la demande de souscription d’ODIRNANE (dans le cas où la souscription est effectuée à la demande de la Société) et (ii) la date de souscription d’ODIRNANE (dans le cas où la souscription est effectuée à la discrétion de l’Investisseur), et concernant les tranches suivantes, aucune ODIRNANE ne doit être en circulation ; vi. la Société dispose d’un nombre d’actions autorisé et disponible égal à au moins (i) 2 fois le nombre d’actions à émettre sur exercice du Droit à l’Attribution des ODIRNANE à émettre et en circulation (sur la base du prix d’attribution applicable à la date de demande de souscription des ODIRNANE) plus (ii) 1 fois le nombre d’actions à émettre sur exercice des BSA à émettre ; 1 D’un commun accord entre la Société et YA II PN, Ltd., ce dernier pourra souscrire des actions nouvelles pour 250 k€ supplémentaires, avant l’émission de la première tranche d’ODIRNANE, à un prix égal à 75% du plus bas cours quotidien moyen pondéré par les volumes de l’action de la Société parmi les jours de bourse au cours desquels YA II PN, Ltd. n’aura pas vendu d’actions de la Société parmi les dix (10) jours de bourse consécutifs précédant immédiatement la date d’émission des actions. 2 Les actionnaires ayant signé l’engagement de conservation représentent environ 65% du capital de la Société : NGN BioMed Opportunity II, L.P., SOFINNOVA CAPITAL, Entities affiliated with Edmond de Rothschild Investment Partners SCA, certain entities affiliated with Seventure Partners, DEWB Deutsche Effecten- und Wechsel-Beteiligungsgesellschaft AG, CD-Venture GmbH, Entities affiliated with TVM Capital GmbH, VC Fonds Berlin GmbH & VC Fonds Technologie Berlin GmbH 5 Kreos Capital récupérera ses droits sur la Dette Kreos notamment dans les cas suivants : (1) suite à un cas de défaut sur les ODIRNANE et à la demande de YA II PN, Ltd. du remboursement en cash des ODIRNANE en circulation, les ORDINANE ne seraient pas remboursées par la Société dans un délai de 14 jours suivant la demande de remboursement, (2) aucune ODIRNANE reste en circulation et aucune ODIRNANE n’a été émise dans les trois mois suivant le dernier remboursement ou conversion d’ODIRNANE et (3) toutes les ODIRNANE prévues dans l’accord entre YA II PN, Ltd. et la Société ont été émises et remboursées ou converties en totalité.


BOWIE, MD / ACCESSWIRE / May 5, 2017 / Erin Lyddane, Senior Vice President - Operations of Old Line Bank (NASDAQ: OLBK), was honored with an Achievement Award at the Fifth Annual Conference of the Maryland Bankers Association's Council of Professional Women in Banking and Finance, held on Thursday, May 4, 2017 at Martin's West in Baltimore. In bestowing this award upon Ms. Lyddane, the Council stated, "This award recognizes your outstanding achievements in your banking career and the leadership and professional impact you have demonstrated, as well as your community service outside your career, which truly embodies the qualities of what the Council of Professional Women in Banking and Finance Achievement Award stands for." James W. Cornelsen, President and Chief Executive Officer of Old Line Bancshares, stated, "Old Line Bank is extremely proud to have Erin recognized by her peers for the excellence that we have had the benefit of observing on a daily basis over many years. Erin exemplifies one of the greatest benefits of a career in Community Banking. She started her career as a teller and has continuously grown in knowledge and responsibility to reach the position of Senior Vice President. She now heads up our Deposit Operations, is the primary owner of our relationship with our core processor, serves as our BSA officer and has taken ownership of our Cyber Risk Assessment and Management program." Old Line Bancshares is the parent company of Old Line Bank, a Maryland chartered commercial bank headquartered in Bowie, Maryland, approximately 10 miles east of Andrews Air Force Base and 20 miles east of Washington, D.C. Old Line Bank has 21 branches located in its primary market area of suburban Maryland (Washington, D.C. suburbs, Southern Maryland and Baltimore suburbs) counties of Anne Arundel, Baltimore, Calvert, Carroll, Charles, Montgomery, Prince George's, and St. Mary's. It also targets customers throughout the greater Washington, D.C. and Baltimore metropolitan areas.


BOWIE, MD / ACCESSWIRE / May 5, 2017 / Erin Lyddane, Senior Vice President - Operations of Old Line Bank (NASDAQ: OLBK), was honored with an Achievement Award at the Fifth Annual Conference of the Maryland Bankers Association's Council of Professional Women in Banking and Finance, held on Thursday, May 4, 2017 at Martin's West in Baltimore. In bestowing this award upon Ms. Lyddane, the Council stated, "This award recognizes your outstanding achievements in your banking career and the leadership and professional impact you have demonstrated, as well as your community service outside your career, which truly embodies the qualities of what the Council of Professional Women in Banking and Finance Achievement Award stands for." James W. Cornelsen, President and Chief Executive Officer of Old Line Bancshares, stated, "Old Line Bank is extremely proud to have Erin recognized by her peers for the excellence that we have had the benefit of observing on a daily basis over many years. Erin exemplifies one of the greatest benefits of a career in Community Banking. She started her career as a teller and has continuously grown in knowledge and responsibility to reach the position of Senior Vice President. She now heads up our Deposit Operations, is the primary owner of our relationship with our core processor, serves as our BSA officer and has taken ownership of our Cyber Risk Assessment and Management program." Old Line Bancshares is the parent company of Old Line Bank, a Maryland chartered commercial bank headquartered in Bowie, Maryland, approximately 10 miles east of Andrews Air Force Base and 20 miles east of Washington, D.C. Old Line Bank has 21 branches located in its primary market area of suburban Maryland (Washington, D.C. suburbs, Southern Maryland and Baltimore suburbs) counties of Anne Arundel, Baltimore, Calvert, Carroll, Charles, Montgomery, Prince George's, and St. Mary's. It also targets customers throughout the greater Washington, D.C. and Baltimore metropolitan areas. BOWIE, MD / ACCESSWIRE / May 5, 2017 / Erin Lyddane, Senior Vice President - Operations of Old Line Bank (NASDAQ: OLBK), was honored with an Achievement Award at the Fifth Annual Conference of the Maryland Bankers Association's Council of Professional Women in Banking and Finance, held on Thursday, May 4, 2017 at Martin's West in Baltimore. In bestowing this award upon Ms. Lyddane, the Council stated, "This award recognizes your outstanding achievements in your banking career and the leadership and professional impact you have demonstrated, as well as your community service outside your career, which truly embodies the qualities of what the Council of Professional Women in Banking and Finance Achievement Award stands for." James W. Cornelsen, President and Chief Executive Officer of Old Line Bancshares, stated, "Old Line Bank is extremely proud to have Erin recognized by her peers for the excellence that we have had the benefit of observing on a daily basis over many years. Erin exemplifies one of the greatest benefits of a career in Community Banking. She started her career as a teller and has continuously grown in knowledge and responsibility to reach the position of Senior Vice President. She now heads up our Deposit Operations, is the primary owner of our relationship with our core processor, serves as our BSA officer and has taken ownership of our Cyber Risk Assessment and Management program." Old Line Bancshares is the parent company of Old Line Bank, a Maryland chartered commercial bank headquartered in Bowie, Maryland, approximately 10 miles east of Andrews Air Force Base and 20 miles east of Washington, D.C. Old Line Bank has 21 branches located in its primary market area of suburban Maryland (Washington, D.C. suburbs, Southern Maryland and Baltimore suburbs) counties of Anne Arundel, Baltimore, Calvert, Carroll, Charles, Montgomery, Prince George's, and St. Mary's. It also targets customers throughout the greater Washington, D.C. and Baltimore metropolitan areas.


News Article | April 27, 2017
Site: globenewswire.com

                   Paris, France - 27 avril 2017 - Le Directoire de Diaxonhit (Alternext : ALEHT, FR0004054427), groupe français leader sur le marché du diagnostic in vitro de spécialités dans les domaines de la transplantation, des maladies infectieuses et de l'oncologie, s'est réuni le 26 avril 2017 et a arrêté les comptes consolidés au 31 décembre 2016. Ces comptes ont été vérifiés par le Conseil de Surveillance2. La transition engagée dès l'été 2016 a entrainé un certain nombre de charges financières et exceptionnelles qui sont notamment liées au plan de réorientation et au plan de réduction de la dilution mis en oeuvre, pour un montant global d'environ 1 M€. Ces facteurs expliquent le résultat net en retrait à -7,9 M€, incluant tous les amortissements liés à l'acquisition d'Ingen, et à -9,6 M€ pro forma, incluant tous les frais financiers et amortissements liés aux acquisitions d'Ingen et de Capforce Plus. Les ventes annuelles de produits de diagnostic in vitro s'inscrivent dans la fourchette annoncée en janvier 2017. Elles s'élèvent ainsi à 27,6 M€ contre 28,9 M€ en 2015, et reflètent le retard dans la disponibilité des nouveaux tests NGS pour le typage HLA et le ralentissement des commandes de tests transplantation à cause des contraintes budgétaires des laboratoires hospitaliers, partiellement compensés par la bonne progression des autres secteurs du diagnostic et du contrôle qualité. Par ailleurs, les produits de R&D thérapeutique se sont élevés à 0,1 M€, en diminution par rapport à 2015 où la Société avait reçu un paiement d'étape non-récurrent d'Allergan de 0,4 M€. Sur une base pro forma, intégrant les résultats 2016 de la société Capforce Plus et de ses filiales comme si elles avaient été acquises le 1er janvier 2016, le chiffre d'affaires annuel s'élève à 44,1 M€, et le montant des revenus annuels à 45 M€. La réduction du coût d'achat des marchandises est directement liée à la baisse des ventes de produits de diagnostic in vitro. Toutefois ce coût d'achat reste affecté par la poursuite du renchérissement du dollar US. Compte-tenu des caractéristiques des contrats d'achat à terme de dollars US détenus par Diaxonhit, le taux de change moyen des dollars achetés en 2016 s'est établi à 1,1463 dollars US par euro contre 1,2173 en 2015. A taux de change constant entre 2015 et 2016, le coût d'achat des marchandises aurait ainsi été inférieur d'environ 0,9 M€. Il est rappelé que les actifs commerciaux réévalués consécutivement à l'acquisition d'IBS font l'objet d'un amortissement sur 10 ans, soit 1 286 K€ au 31 décembre 2016. Ils sont inclus dans les frais marketing et commerciaux. De même, depuis le début de la commercialisation de BJI Inoplex, un actif R&D relatif à ce test et également réévalué consécutivement à l'acquisition d'IBS, fait l'objet d'un amortissement sur 10 ans, soit 98 K€ au 31 décembre 2016, inclus dans les frais de R&D. L'écart d'acquisition restant fait aussi l'objet d'un amortissement sur 10 ans qui vient en déduction du résultat opérationnel et représente, au 31 décembre 2016, une charge de 308 K€. L'ensemble de ces amortissements représente une charge sans effet sur la trésorerie de la Société. Au 31 décembre 2015, Diaxonhit disposait d'une trésorerie de 11,7 M€. Compte-tenu de financements reçus de 0,5 M€ nets des charges d'intérêts et remboursements intervenus sur les obligations, les emprunts et les avances remboursables de la Société, et d'une consommation de trésorerie opérationnelle de 3,3 M€, la trésorerie du Groupe s'élève à 7,9 M€ au 31 décembre 2016. Diaxonhit détient la licence exclusive du test AlloMap® pour l'Europe. En janvier 2016, Diaxonhit et CareDx Inc. ont finalisé avec succès le transfert du test d'expression génomique AlloMap pour la surveillance régulière et non invasive du rejet cellulaire aigu chez les greffés cardiaques, au Laboratoire Central d'Immunologie des Hôpitaux Universitaires de Strasbourg (HUS) en France. Ce transfert a été réalisé en plusieurs étapes qui ont démontré que les résultats des tests AlloMap effectués par le laboratoire des HUS sont les mêmes que ceux qui ont été obtenus par le laboratoire principal de CareDx aux États-Unis. C'est une étape importante pour Diaxonhit et CareDx, tout en étant le premier transfert de ce type pour un test moléculaire développé et déjà commercialisé aux USA. En mai 2016, Diaxonhit et les HUS ont inauguré le centre de traitement des tests AlloMap. Ce centre répond à toutes les exigences de qualité nécessaires pour assurer la précision et la reproductibilité des résultats rendus aux prescripteurs. La Société lui fournit les éléments du test produits par CareDx et lui met également à disposition les instruments nécessaires à la réalisation du test. Diaxonhit fournit aussi aux centres de transplantation cardiaque européens un kit pour réaliser la préparation des échantillons de sang et leur expédition. Dans le cadre de cette étude, dont les résultats sont attendus au cours de l'année 2017, 1 700 prélèvements à l'aiguille fine ont été effectués sur des nodules thyroïdiens découverts chez les 1 581 patients recrutés dans 17 centres cliniques européens (10 en France, 4 en Italie et 3 en Espagne) spécialisés dans le diagnostic et le suivi du cancer de la thyroïde. Avec ces caractéristiques, l'étude CITHY est la plus grosse étude de ce type et une première en Europe qui va également permettre de mieux caractériser les pratiques européennes de suivi des patients présentant un ou plusieurs nodules de la thyroïde. Une nouvelle étude prospective en vie réelle a été réalisée à l'hôpital Raymond-Poincaré (AP-HP) de Garches et à l'hôpital Joseph-Ducuing de Toulouse. Elle a porté sur l'utilisation en routine de BJI InoPlex, avec 361 tests réalisés sur 314 patients plus représentatifs de la population ciblée dans les centres de deuxième ligne. Pour les 80 patients avec une infection chronique à staphylocoque, la performance de BJI InoPlex est améliorée par rapport à celle observée dans l'étude de validation du test. Par ailleurs, les résultats du test BJI InoPlex et de la mise en culture de ponctions articulaires réalisées avant chirurgie, qui avaient été obtenus dans le cadre de l'étude initiale de validation, ont fait l'objet d'une analyse complémentaire en excluant les 72 patients pour lesquels aucune ponction n'avait été réalisée ou pour lesquels le résultat de BJI InoPlex était indéterminé. Cette nouvelle analyse montre d'une part que les résultats de culture sur ponctions articulaires réalisées avant intervention chirurgicale ne sont pas aussi fiables qu'il est généralement admis. Ils montrent aussi clairement que cette fiabilité peut être améliorée en combinant la microbiologie classique à BJI InoPlex. Pendant l'année 2016, DIAXONHIT collaborait avec la société de biotechnologie InnaVirVax dans le cadre d'un consortium ayant pour objectif la mise au point de VAC-3S, un vaccin thérapeutique pour traiter les malades atteints du Sida, et le développement d'un test diagnostique compagnon du vaccin, dont le prototype avait été finalisé en cours d'année.                   InnaVirVax vient d'annoncer à la Société que les résultats de sa dernière étude clinique étaient médiocres. Sur cette base, InnaVirVax a pris la décision d'interrompre définitivement le développement de VAC-3S, et en a notifié Bpifrance et les membres du consortium Prothevih. En conséquence, le développement du test compagnon de VAC-3S est également arrêté par Diaxonhit. La Société évalue actuellement les conséquences de cet arrêt, et en particulier l'utilité de poursuivre le développement du test indépendamment du vaccin thérapeutique.                     Afin de réduire la dilution future des actionnaires de Diaxonhit, quatre transactions spécifiques ont été réalisées en deux temps.                   Au cours de l'exercice 2016, la société a réalisé tout d'abord des amortissements en numéraire d'obligations convertibles émises en juin 2014 (OCA), pour un total de 383 K€. D'autre-part, elle a procédé au rachat en numéraire de 6.158.000 bons de souscription qui avaient également été émis en juin 2014 (BSA), pour 537 K€. Ce dernier montant a constitué une charge financière exceptionnelle sur l'exercice 2016.                   Depuis le 1er janvier 2017, et notamment dans le cadre de la finalisation de l'acquisition de Capforce Plus, Diaxonhit a procédé à deux nouveaux amortissements en numéraire d'OCA pour un montant total de 525 K€, puis racheté 5.953.470 BSA.  Cette restructuration globale a entrainé l'émission de 3.453.012 actions nouvelles.                   Sur la base d'un amortissement par émission d'actions au cours de 0,22€ par actions, les amortissements effectués en numéraire en 2016 et depuis le début de l'année 2017, se seraient traduits par l'émission de 4.127.093 actions supplémentaires. Cumulé aux transactions effectuées sur les BSA, c'est un total de 12.785.551 actions qui ne seront plus émises, soit environ 7% du capital actuel.                     Fort de ses 120 collaborateurs, le nouveau groupe Diaxonhit, acteur intégré français du diagnostic in vitro, intervient de la recherche à la commercialisation de produits diagnostiques de spécialités et désormais également de produits pour la recherche dans le domaine des sciences de la vie. D'autre-part, son expansion continue à s'appuyer à la fois sur la croissance de ses activités commerciales de distribution et sur le développement de produits propriétaires et innovants à forte valeur ajoutée.         Diaxonhit possède un portefeuille étendu et diversifié de produits propriétaires dans quatre spécialités : la transplantation, les maladies infectieuses, les sciences du vivant et le cancer.                   Dans le domaine de la transplantation, le groupe commercialise des milieux de transport et de préservation des greffons de cornée ainsi qu'un dispositif breveté, Iglide(TM), pour en faciliter la mise en oeuvre chirurgicale. Il commercialise également Allomap, un test moléculaire pour le suivi des transplantés cardiaques, dont il détient la licence exclusive pour l'Europe.                   Dans le domaine des maladies infectieuses, le groupe commercialise plusieurs produits propriétaires et notamment TQS pour l'identification du statut immunitaire vis-à-vis du tétanos, BJI Inoplex pour le diagnostic des infections ostéo-articulaires sur prothèse, ainsi que la gamme de biologie moléculaire Eurobioplex (EBX) qui comprend un ensemble de tests permettant d'identifier de nombreux agents pathogènes et d'en évaluer la quantité présente dans l'organisme des patients infectés.                   Dans le domaine des sciences de la vie, le groupe développe un ensemble de produits destinés à la R&D, en particulier auprès d'organismes publics de recherche et de l'industrie pharmaceutique. Il commercialise notamment des milieux de culture cellulaires, des réactifs de biologie moléculaire ainsi que des anticorps propriétaires. Doté d'un laboratoire et d'une forte expertise industrielle, le groupe propose un service de production à façon dédié aux sociétés de biotechnologie ou pharmaceutiques.                   Par ailleurs, Diaxonhit développe d'autres produits sur la base de sa plateforme de biologie moléculaire, en particulier Dx15 pour le diagnostic du cancer de la thyroïde. A travers ses filiales commerciales, Eurobio et Ingen, le groupe renforce aujourd'hui sa position de 1er distributeur indépendant français de diagnostics in vitro sur son territoire.                   Dans ce cadre, il commercialise des tests de diagnostic de spécialité auprès des laboratoires d'analyses de biologie médicale hospitaliers et privés. Il est ainsi le leader en France du marché des tests HLA pour la transplantation. Il commercialise également en exclusivité des tests et des solutions automatisées issus de partenaires industriels étrangers (américains, coréens, européens.) dans les domaines des maladies infectieuses, de l'auto-immunité et des contrôles qualité. Il propose aussi toute une gamme de réactifs et d'instruments dédiés aux laboratoires des sciences de la vie.                   S'appuyant sur ses ingénieurs et spécialistes produits, le groupe assure également un service client haut-de-gamme, avec assistance téléphonique, support technique et service après-vente pour une importante base de plus de 400 instruments installés dans les laboratoires de ses clients. Diaxonhit (Alternext, FR0004054427, ALEHT) est un acteur majeur dans le domaine du diagnostic in vitro de spécialités et des sciences de la vie. Il intervient de la recherche à la commercialisation de tests diagnostiques dans les domaines de la transplantation, des maladies infectieuses et de l'oncologie, ainsi que de produits pour la recherche dans le domaine des sciences du vivant. Il est notamment le leader en France de la commercialisation des tests HLA. Avec ses nombreux partenariats et sa forte présence hospitalière, Diaxonhit dispose de son propre réseau étendu de distribution et d'un portefeuille de produits propriétaires parmi lesquels Tétanos Quick Stick®, BJI Inoplex®, et la gamme de biologie moléculaire EBX (Dengue, Chickungunya, Zika, Hépatite delta, etc.) dans le domaine des maladies infectieuses. Dans le domaine des sciences de la vie, le groupe développe un ensemble de produits destinés à la R&D, en particulier auprès d'organismes publics de recherche et de l'industrie pharmaceutique. Il commercialise notamment des milieux de culture cellulaires, des réactifs de biologie moléculaire ainsi que des anticorps propriétaires, et propose un service de production à façon dédié aux sociétés de biotechnologie ou pharmaceutiques. Diaxonhit produit et commercialise également des milieux de transport et de préservation des greffons de cornée ainsi qu'un dispositif breveté, Iglide(TM), pour en faciliter la mise en oeuvre chirurgicale. La Société est membre du GIE européen DiaMondial. Ce communiqué comporte des éléments non factuels, notamment et de façon non exclusive, certaines affirmations concernant des résultats à venir et d'autres événements futurs. Ces affirmations sont fondées sur la vision actuelle et les hypothèses de la Direction de la Société. Elles incorporent des risques et des incertitudes connues et inconnues qui pourraient se traduire par des différences significatives au titre des résultats, de la rentabilité et des événements prévus. En outre, Diaxonhit, ses actionnaires et ses affiliés, administrateurs, dirigeants, conseils et salariés respectifs n'ont pas vérifié l'exactitude des, et ne font aucune déclaration ou garantie sur, les informations statistiques ou les informations prévisionnelles contenues dans le présent communiqué qui proviennent ou sont dérivées de sources tierces ou de publications de l'industrie; ces données statistiques et informations prévisionnelles ne sont utilisées dans ce communiqué qu'à des fins d'information. Enfin, le présent communiqué peut être rédigé en langue française et en langue anglaise. En cas de différences entre les deux textes, la version française prévaudra.


News Article | April 17, 2017
Site: news.yahoo.com

Former Afghan President Hamid Karzai speaks during an interview with the Associated Press in Kabul, Afghanistan, Monday, April 17, 2017. Karzai said that the U.S. is using Afghanistan as a weapons testing ground, calling the recent use of the largest-ever non-nuclear bomb “an immense atrocity against the Afghan people.” Last week, U.S. forces dropped the GBU-43 Massive Ordnance Air Blast (MOAB) bomb in Nangarhar province, reportedly killing 95 militants. (AP Photo/Rahmat Gul) KABUL, Afghanistan (AP) — Former Afghan President Hamid Karzai said Monday that the U.S. is using Afghanistan as a weapons testing ground, calling the recent use of the largest-ever non-nuclear bomb "an immense atrocity against the Afghan people." Last week, U.S. forces dropped the GBU-43 Massive Ordnance Air Blast (MOAB) bomb in eastern Nangarhar province, reportedly killing 95 militants. Karzai, in an interview with The Associated Press, objected to the decision, saying that his country "was used very disrespectfully by the U.S. to test its weapons of mass destruction." The office of President Ashraf Ghani said following the bomb's usage that there was "close coordination" between the U.S. military and the Afghan government over the operation, and they were careful to prevent any civilian casualties. But Karzai harshly criticized the Afghan government for allowing the use of the bomb. "How could a government of a country allow the use of a weapon of mass destruction on its own territory? Whatever the reason, whatever the cause, how could they allow that? It just unimaginable," he said. The strike was carried out Thursday morning against an Islamic State group tunnel complex, carved into a mountain that Afghan forces had tried to assault repeatedly in recent weeks, according to Afghan officials. U.S. and Afghan forces have been battling the Taliban for more than 15 years. But the U.S. military unveiled the largest conventional bomb in its arsenal against the Islamic State group, which has a far smaller but growing presence in Afghanistan. U.S. President Donald Trump has publicly vowed to aggressively confront IS. Trump called the operation a "very, very successful mission" but Karzai had harsh words for the new U.S. leader. "My message to President Trump today is that he has committed an immense atrocity against the Afghan people, against fellow human beings," he said. "If the American government sees us as human beings, then they have committed a crime against fellow human beings, but if they treat us as less than human beings, well, of course they can do whatever they want." Karzai added that one of the fundamental reasons that he refused to sign the bilateral security agreement with the United States when he was the president was specifically to prevent such actions. "I told the people of Afghanistan in the Loya Jirga (Grand Assembly) we must not sign the BSA with the U.S., that we must not give them bases till the day they bring peace to Afghanistan," he said. "Why would the Afghan people want to give the U.S. bases? For what? To continue the war in Afghanistan, to become more insecure, to lose peace forever, to suffer, to receive more bombs, to receive a weapon of mass destruction? Or for security, for peace and for a better life?" The U.S. National Security Adviser H. R. McMaster met with President Ghani during a visit to Afghanistan on Sunday. According to statement from the office of the president, the pair discussed mutual counterterrorism efforts, security and economic development. The U.S. estimates 600-800 IS fighters are in Afghanistan, mostly in Nangarhar. American forces have concentrated on fighting them while also supporting Afghan forces against the Taliban. The U.S. has more than 8,000 troops on the ground in Afghanistan, training local forces and conducting counterterrorism operations.


No statistical methods were used to predetermine sample size. The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. Male heterozygous ythdf2+/− fish in the *AB background were custom made by ZGeneBio. TALEN mutagenesis was performed to mutate ythdf2 (Ensembl ENSDART00000127043) with L1 recognition sequence 5′-GGACCTGGCCAATCCCC-3′, R1 recognition sequence 5′-GGCACAGTAATGCCACC-3′, and spacer sequence 5′-TCCCAATTCAGGAATG-3′. Purchased fish were outcrossed to in-house wild-type *AB fish. Embryos were obtained from natural crosses, were raised under standard conditions, and were staged according to literature26. Embryos were reared at 28.5 °C and all experiments and observations were performed as close to this temperature as possible. Fish lines were maintained in accordance with AAALAC research guidelines, under a protocol approved by the University of Chicago IACUC (Institutional Animal Care & Use Committee). The open reading frame of zebrafish ythdf2 was purchased from Open Biosystems (clone 5601005) and subcloned into a pCS2+ vector using restriction enzyme sites of BamHI and XhoI. The resulting vector was linearized by HindIII and used as a template for ythdf2 probe preparation. Antisense digoxigenin (DIG) RNA probes were generated by in vitro transcription using standard reagents and methods. In situ hybridization protocol was followed essentially as previously reported27. All experiments were repeated at least once from biological samples. Control and ythdf2 morpholinos (5′-TGGCTGACATTTCTCACTCCCCGGT-3′) were obtained from Gene Tools (Oregon). 3 ng of either control or gene-specific morpholino was injected into *AB wild-type embryos at the one-cell stage. GFP and mCherry were subcloned into pCS2+ vectors and linearized by NotI. GFP-m6A, GFP-A, and mCherry-capped and polyadenylated mRNA was generated by in vitro transcription using mMessage mMachine SP6 kit (Thermo Fisher) and Poly(A) tailing kit (Thermo Fisher) according to the manufacturer’s protocol. Products were purified with the MEGAclear transcription clean-up kit (Thermo Fisher) and used for injections directly. For GFP-m6A, we spiked 6 nmol m6ATP into the 100 nmol ATP supplied in the transcription reaction, in order to ensure that less than 0.3% of GFP mRNAs are without m6A on average. (GFP mRNA is 942 nt; each mRNA has 1.89 m6A on average.) 35 pg of either GFP reporter mRNA and 10 pg of mCherry mRNA were injected together in 1.25 nl into embryos at the one-cell stage. ythdf2 mRNA containing the ythdf2 5′ UTR and a 3′ Flag tag, which was used to rescue the mutant phenotype and validate the knockdown efficiency of ythdf2 MO, was constructed in pCS2+ vector (forward primer: 5′-CGTACGGATCCTGTCTGATCTGCAGCTGTAG-3′; reverse primer: 5′-CGATGCTCGAGTTACTTGTCATCGTCGTCCTTGTAATCTATTCCAGATGGAGCAAGGC-3′) and prepared in the same way as mCherry mRNAs. Antibodies used in this study are listed below in the format of name (application; catalogue number; supplier): mouse anti-Flag HRP conjugate (Western; A5892; Sigma), rabbit anti-m6A (m6A-seq and m6A-CLIP-seq; 202003; Synaptic Systems), rabbit anti-histone H3 (IF; ab5176; Abcam), and anti-rabbit Alexa Fluor 488 (IF; ab150077; Abcam). All images were observed with a Leica MZFLIII microscope and captured with a Nikon D5000 digital camera using Camera Control Pro (Nikon) software. For fluorescent microscopy, standard ET-GFP and TXR LP filters (Leica) were used. For bright field imaging of live embryos, only saturation was adjusted and was adjusted identically for all images. For fluorescent imaging of live embryos, no image processing was performed. For fluorescent imaging of fixed embryos, contrast and exposure were adjusted for all to obtain the lowest amount of background while preserving the morphology of all visible nuclei. All experiments were repeated at least once from biological samples. To compare the total amount of DNA in wild-type and mutant embryos at different time points during the MZT, 10 embryos per time point per condition were dechorionated and pipetted into standard DNA lysis buffer. The number of embryos in each tube was counted twice to ensure uniformity. Proteinase K was added to 100 μg ml−1 and the embryos were incubated for 4 h at ~55 °C with occasional mixing. Proteinase K was inactivated by a 10-min incubation at 95 °C and the DNA was then phenol-chloroform-extracted, ethanol-precipitated, and resuspended in 100 μl Tris (pH 8.5) and 1 mM EDTA using standard procedures. Double-stranded DNA content was measured with NanoDrop. Three biological replicates (comprised of the offspring of three different fish mating pairs of the appropriate genotype) were measured for each time point for both the control and experimental samples. Biological replicates were averaged together to determine the average DNA amount per time point per genotype and to compute standard errors of the mean. All DNA values were normalized to that of wild-type embryos at 2.5 h.p.f. Embryos were collected into standard 2× protein sample buffer with added β-mercaptoethanol and protease inhibitors and immediately put on ice for a few minutes. The embryo mixtures were carefully but thoroughly pipetted up and down to dissolve and homogenize the embryos, and then samples were heated at 95 °C for 5 min and frozen at −80 °C. Before use, samples were again heated for 5 min and then centrifuged at 12,000 r.p.m. to remove debris. Supernatants were loaded into a 10-well, 1.5 mm Novex 4–20% Tris-Glycine Mini Protein Gel (Thermo Fisher) with 6 embryos per well. The gel was transferred onto a nitrocellulose membrane using iBlot2 gel transfer system (Thermo Fisher) set to P3 for 7 min with iBlot2 mini gel transfer stacks (Thermo Fisher). Membranes were blocked in 5% BSA, 0.05% Tween-20 in PBS for 1 h, and then incubated overnight at 4 °C with anti-Flag–HRP conjugate (Sigma) diluted 1:10,000 in 3% BSA. Proteins were visualized using the SuperSignal West Pico Luminol/Enhancer solution (Thermo Fisher) in FluorChem M system (ProteinSimple). mRNA isolation for LC-MS/MS: total RNA was isolated from zebrafish embryos with TRIzol reagent (Invitrogen) and Direct-zol RNA MiniPrep kit (Zymo). mRNA was extracted by removal of contaminating rRNA using RiboMinus Eukaryote Kit v2 (Thermo Fisher) for two rounds. Total RNA isolation for RT–qPCR: we followed the instruction of Direct-zol RNA MiniPrep kit (Zymo) with DNase I digestion step. Total RNA was eluted with RNase-free water and used for RT–qPCR directly. 100–200 ng of mRNA was digested by nuclease P1 (2 U) in 25 μl of buffer containing 10 mM of NH OAc (pH 5.3) at 42 °C for 2 h, followed by the addition of NH HCO (1 M, 3 μl, freshly made) and alkaline phosphatase (0.5 U). After an additional incubation at 37 °C for 2 h, the sample was diluted to 50 μl and filtered (0.22 μm pore size, 4 mm diameter, Millipore), and 5 μl of the solution was injected into LC-MS/MS. Nucleosides were separated by reverse-phase ultra-performance liquid chromatography on a C18 column with on-line mass spectrometry detection using an Agilent 6410 QQQ triple-quadrupole LC mass spectrometer in positive electrospray ionization mode. The nucleosides were quantified by using the nucleoside to base ion mass transitions of 282 to 150 (m6A), and 268 to 136 (A). Quantification was performed in comparison with the standard curve obtained from pure nucleoside standards running on the same batch of samples. The ratio of m6A to A was calculated on the basis of the calibrated concentrations9. Total RNA was isolated from fish embryos collected at different time points with TRIzol reagent and Direct-zol RNA MiniPrep kit. For each time point, ~200 embryos were collected to ensure RNA yield and that samples were representative. mRNA was further purified using RiboMinus Eukaryote Kit v2. RNA fragmentation was performed by sonication at 10 ng μl−1 in 100 μl RNase-free water using Bioruptor Pico (Diagenode) with 30 s on/off for 30 cycles. m6A-immunoprecipitation (IP) and library preparation were performed according to the previous protocol17. Sequencing was carried out on Illumina HiSeq 2000 according to the manufacturer’s instructions. Additional high-throughput sequencing of zebrafish methylome was carried out using a modified m6A-seq method, which is similar to previously reported methods19, 20. Briefly, total RNA and mRNA were purified as previously described for m6A-seq. Purified mRNA (1 μg) was mixed with 2.5 μg of affinity purified anti-m6A polyclonal antibody (Synaptic Systems) in IPP buffer (150 mM NaCl, 0.1% NP-40, 10 mM Tris-HCl (pH 7.4)) and incubated for 2 h at 4 °C. The mixture was subjected to UV-crosslinking in a clear flat-bottom 96-well plate (Nalgene) on ice at 254 nm with 0.15 J for 3 times. The mixture was then digested with 1 U μl−1 RNase T1 at 22 °C for 6 min followed by quenching on ice. Next, the mixture was immunoprecipitated by incubation with protein-A beads (Invitrogen) at 4 °C for 1 h. After extensive washing, the mixture was digested again with 10 U μl−1 RNase T1 at 22 °C for 6 min followed by quenching on ice. After additional washing and on-bead end-repair, the bound RNA fragments were eluted from the beads by proteinase K digestion twice at 55 °C for 20 and 10 min, respectively. The eluate was further purified using RNA clean and concentrator kit (Zymo Research). RNA was used for library generation with NEBNext multiplex small RNA library prep kit (NEB). Sequencing was carried out on Illumina HiSeq 2000 according to the manufacturer’s instructions. Total RNA was isolated from wild-type and mutant fish embryos collected at different time points with TRIzol reagent and Direct-zol RNA MiniPrep kit. For each time points, ~20 embryos were collected to ensure RNA yield and that samples were representative. mRNA was further purified using RiboMinus Eukaryote Kit v2. RNA fragmentation was performed using Bioruptor Pico as described previously. Fragmented mRNA was used for library construction using TruSeq stranded mRNA library prep kit (Illumina) according to manufacturer’s protocol. Sequencing was carried out on Illumina HiSeq 2000 according to the manufacturer’s instructions. All samples were sequenced by Illumina Hiseq 2000 with single-end 50-bp read length. The deep-sequencing data were mapped to zebrafish genome version 10 (GRCz10). (1) For m6A-seq, reads were aligned to the reference genome (danRer10) using Tophat v2.0.14 (ref. 28) with parameter -g 1–library-type = fr-firststrand. RefSeq Gene structure annotations were downloaded from UCSC Table Browser. The longest isoform was used if the gene had multiple isoforms. Aligned reads were extended to 150 bp (average fragments size) and converted from genome-based coordinates to isoform-based coordinates, in order to eliminate the interference from introns in peak calling. The peak-calling method was modified from published work18. To call m6A peaks, the longest isoform of each gene was scanned using a 100 bp sliding window with 10 bp step. To reduce bias from potential inaccurate gene structure annotation and the arbitrary usage of the longest isoform, windows with read counts less than 1 out of 20 of the top window in both m6A-IP and input sample were excluded. For each gene, the read counts in each window were normalized by the median count of all windows of that gene. A Fisher exact test was used to identify the differential windows between IP and input samples. The window was called as positive if the FDR < 0.01 and log (enrichment score) ≥ 1. Overlapping positive windows were merged. The following four numbers were calculated to obtain the enrichment score of each peak (or window): (a) reads count of the IP samples in the current peak or window, (b) median read counts of the IP sample in all 100 bp windows on the current mRNA, (c) reads count of the input sample in the current peak/window, and (d) median read counts of the input sample in all 100 bp windows on the current mRNA. The enrichment score of each window was calculated as (a × d)/(b × c). (2) For m6A-CLIP-seq, after removing the adaptor sequence, the reads were mapped to the reference genome (danRer10) using Bowtie2. Peak calling method was similar to the previous study19. Briefly, mutations were considered as signal and all mapped reads were treated as background. A Gaussian Kernel density estimation was used to identify the binding regions. The motif analysis was performed using HOMER29 to search motifs in each set of m6A peaks. The longest isoform of all genes was used as background. (3) For mRNA-seq, reads were mapped with Tophat and Cufflink (v2.2.1) was used to calculate the FPKM of each gene to represent their mRNA expression level30. (4) For fish gene group categorization, we used the input mRNA-seq data from m6A-seq. FPKM of all genes were first normalized to the highest value of five time points, with only genes with FPKM >1 analysed. Then Cluster3.0 (ref. 31) was used to divide all genes into six clusters, with the parameters: adjust data – normalize genes; k-means cluster – organize genes, 6 clusters, 100 number; k-means – Euclidean distance. The result clustered file with clustered number was merged with original FPKM values, imported and processed in R, and plotted in Excel. (5) For GO analysis, the list of target genes was first uploaded into DAVID32, 33 and analysed with functional annotation clustering. The resulting file was downloaded and extracted with GO terms and corresponding P values. The new list (contains GO terms with P < 0.01) was imported into REVIGO34 and visualized with the interactive graph, which was used as the final output figures. Methylated genes (at each time point) were defined as overlapped gene targets between m6A-seq and m6A-CLIP-seq. Ythdf2-regulated genes were defined as overlapped gene targets between the lists of the top 20% upregulated genes in both ythdf2 knockout and MO-injected samples. The most stringent Ythdf2 target genes at 4 h.p.f. (135) were defined in the main text, as overlapped genes of methylated genes at 4 h.p.f. (3,237) and Ythdf2-regulated genes at 4 h.p.f. (876). All the raw data and processed files have been deposited in the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) and accessible under GSE79213. A summary of sequenced samples and processed FPKM data are included as Supplementary Data 2. One set of representative experiment results from at least two independent experiments were shown where applicable. Quantitative reverse-transcription PCR (RT–qPCR) was performed to assess the relative abundance of mRNA. All RNA templates used for RT–qPCR were pre-treated with on-column DNase I digestion in the purification step. RT–qPCR primers were designed to span exon-exon junctions to only detect mature mRNA. RT–qPCR was performed by using SuperScript III one-step RT–PCR system (Thermo Fisher) with 50–100 ng total RNA template. Actb1 was used as an internal control as it showed relative invariant expression during the studied time period according to pilot RT–qPCR data. P values were determined using two-sided Student’s t-test for two samples with equal variance. *P < 0.05; **P < 0.01; ***P < 0.001. The sequences of primers used in this study are listed below: actb1: forward 5′-CGAGCAGGAGATGGGAACC-3′, reverse 5′-CAACGGAAACGCTCATTGC-3′; buc: forward 5′-CAAGTTACTGGACCTCAGGATC-3′, reverse 5′-GGCAGTAGGTAAATTCGGTCTC-3′; zgc:162879: forward 5′-TCCTGAATGTCCGTGAATGG-3′, reverse 5′-CCCTCAGATCCACCTTGTTC-3′; mylipa: forward 5′-CCAAACCAGACAACCATCAAC-3′, reverse 5′-CACTCCACCCCATAATGCTC-3′; vps26a: forward 5′-AAATGACAGGAATAGGGCCG-3′, reverse 5′-CAGCCAGGAAAAGTCGGATAG-3′; tdrd1: forward 5′-TACTTCAACACCCGACACTG-3′, reverse 5′-TCACAAGCAGGAGAACCAAC-3′; setdb1a: forward 5′-CTTCTCAACCCAAAACACTGC-3′, reverse 5′-CTATCTGAAGAGACGGGTGAAAC-3′; mtus1a: forward 5′-TGGAGTATTACAAGGCTCAGTG-3′, reverse 5′-TTATGACCACAGCGACAGC-3′; GFP: forward 5′-TGACATTCTCACCACCGTGT-3′, reverse 5′-AGTCGTCCACACCCTTCATC-3′. High-throughput sequencing data that support the findings of this study have been deposited at GEO under the accession number GSE79213. All the other data generated or analysed during this study are included in the article and Supplementary Information.


Patent
Bsa | Date: 2012-04-18

A magazine for an airgun comprising a housing (2) and a magazine rotor (3) rotatably mounted therein. The magazine rotor (3) including a plurality of bores (7) therethrough, each bore forming a chamber (7) for receiving an airgun pellet. The magazine (1) includes an indexing arrangement including a biasing element to index the magazine rotor (3). At least one of the bores (7) includes a lead-in portion (8) adapted and arranged such that when contacted by a bolt of an airgun when the magazine (1) is mounted in an airgun, the magazine rotor (3) is rotated against the force of the biasing element.

Loading BSA collaborators
Loading BSA collaborators