merck serono ( emd serono in the united states and canada ) is a pharmaceutical company headquartered in darmstadt , germany , and a brand and division of merck focused on biopharmaceuticals .

in september 2006 , merck kgaa announced its intent to purchase the majority of serono shares from ernesto bertarelli and the bertarelli family .

the merck-serono merger was announced on 21 september 2006 .

merck kgaa and serono operated as distinct entities until at least january 2007 .

as of january 5 , 2007 , merck held the majority shares of serono .

the new company is called merck serono international sa . in 2012 , merck serono moved its headquarters from geneva , switzerland to darmstadt .

drugs they market include erbitux , uft , rebif , novantrone , gonal , ovidrel/ovitrelle , zorbtive , luveris , saizen , serostim , glucophage , concor and euthyrox .

raptiva was withdrawn in 2007 .

in the u.s. and canada , merck serono is known as emd serono , as the former merck subsidiary merck & co. holds the rights to the name merck in those countries .

merck serono

earlier this month merck serono announced the launch of merck global grants , a program that covers merck serono’s grants for innovation in research as well as grants for independent medical education . the program will invest 20 million pounds for all grants programs in merck serono’s portfolio . the biopharmaceutical division also appointed luciano rossetti as executive vice president and global head of r & d of merck serono earlier this july .
/ - - emd serono , inc . , a subsidiary of merck kgaa , darmstadt ,
emd serono , canada , is founded upon the proud heritage of merck kgaa , darmstadt , germany . in the united states and canada , the division operates as emd serono .
merck’s biopharmaceutical division merck serono announced its collaboration with the institute of experimental neurology ( inspe ) under the san raffaele university and research hospital in milan , italy , to advance research in neurodegenerative diseases .
anthony feinstein has received grant support from the multiple sclerosis society of canada and honoraria from merck - serono , teva , bayerschering and biogen .
alan thompson has received honoraria / support for travel for consulting from btg international , biogen idec , merck serono , eisai ltd , novartis , and honoraria and support for travel for teaching from serono symposia international foundation .
giancarlo comi has received personal compensation for activities with novartis , teva pharmaceutical ind . ltd , sanofi - aventis , merck serono , bayer schering , actelion .
marco salvetti received lecture fees from biogen - dompé , research support from bayer - schering , biogen - dompé , merck - serono , sanofi - aventis .
publication of merck kgaa , darmstadt , germany . in the united states and canada the subsidiaries of merck kgaa , darmstadt , germany operate under the umbrella brand emd .
as part of the agreement , san raffaele university and research hospital will supply its expertise and laboratories to develop new treatments as well as assess the efficacy of merck serono’s molecules .
harsukh parmar , merck serono svp , global head of research and early development , immunology and neurology , said , “merck serono is pleased to continue the collaborative alliance with the san raffaele scientific institute . our translational approach to these disease states and combined commitment to expediting the discovery of new therapies aims to improve health outcomes for patients living with unmet medical needs . ”
there are two different , unaffiliated companies that use the name merck . merck kgaa , darmstadt , germany , which operates this website , uses the firm name
merck kgaa , darmstadt , germany ,
in the united states and canada , and also uses
emd serono
in biopharma ,
milliporesigma
in life science and
emd performance materials
in materials business . the other company , merck & co . , inc . holds the rights in the trademark merck in the united states and canada . merck & co . is not affiliated with or related to merck kgaa , darmstadt , germany , which owns the merck trademark in all other countries of the world . to reflect such fact and to avoid any confusion , certain logos , terms and business description of the publication on this website have been substituted or modified , such as by referring to
merck kgaa , darmstadt , germany
instead of
merck
standing alone . publications on this webpage , therefore , slightly deviate from the otherwise identical versions accessible outside the united states and canada .
merck serono and feinstein institute the research arm of north shore - long island jewish health system in new york have entered into a joint collaboration to develop new antibody based therapies to treat sy . . .
emd serono , canada provides innovative drug therapies that address unmet medical needs in the areas of neurodegenerative diseases , fertility and endocrinology .
raj kapoor has received personal compensation for activities with bayer schering , biogen idec , genzyme , merck serono , ms therapeutics , novartis , and teva , and research support from novartis , the ms society of gb & ni and the national ms society ( usa ) .
emd serono , canada offers medicines , adherence and devices and patient support services in the areas of neurodegenerative diseases , fertility and endocrinology .
around the world , merck kgaa , darmstadt , germany employees are active on all continents , bringing our products to customers in 150 locations & regions .
committed to establishing partnerships to address the unmet needs of patients , emd serono , canada is focused on delivering solutions that improve the quality . . . more
we are the biopharmaceutical division of merck kgaa , darmstadt , germany . we focus exclusively on specialty care - integrating cutting - edge science with industry - leading patient support .
committed to establishing partnerships to address the unmet needs of patients , emd serono , canada is focused on delivering solutions that improve the quality of life for all patients .
in 2011 , domain therapeutics signed an exclusive development and licensing agreement with merck serono , a division of merck kgaa , darmstadt , germany , to develop metabotropic glutamate receptor 4 ( mglur4 ) positive allosteric modulator ( pam ) drugs targeting parkinson’s disease and other neurodegenerative diseases . domain therapeutics has contributed optimized compounds that have been developed from its proprietary chemical series . under the terms of the agreement , the company has received eur 2 million in upfront payment and research funding , and was eligible for up to eur 132 million in milestones for the first two products , as well as undisclosed royalties .
this site contains information that is intended for us residents only . canadian residents should consult the emd serono canada inc . website at urltoken for information on products and services approved in canada .
in 2012 , domain therapeutics has granted prexton therapeutics ( geneva - switzerland ) an exclusive option to license and develop metabotropic glutamate receptor 4 ( mglur4 ) positive allosteric modulator ( pam ) drugs targeting parkinson’s disease . the chemical series was previously developed through a licensing and collaboration agreement signed between domain and merck serono , a division of merck ( darmstadt - germany ) in january 2011 . under the terms of the initial agreement between domain therapeutics and prexton therapeutics - a spin - off company of merck serono - prexton benefited from an exclusive license option to progress the mglur4 pam drug candidates into clinical development . after having exercised the exclusive option , prexton entered into license agreement with domain therapeutics , selected an mglur4 pam candidate , pxt002331 , and conducted regulatory preclinical development and phase i . in september 2016 , prexton announced the successful completion of the phase i clinical trial . in 2017 , prexton initiated a phase ii to assess the safety and effectiveness of foliglurax . the company was acquired early in march 2018 by lundbeck .
in 2017 , domain therapeutics and merck kgaa ( darmstadt , germany ) entered into collaboration and licensing agreement for the development of adenosine receptor antagonist drugs specifically designed for oncology and immuno - oncology . merck will support research activities and gain worldwide rights to domain therapeutics’ next generation of adenosine receptor inhibitors . under the terms of the agreement , domain will be eligible for more than eur 240 million in milestones , as well as undisclosed royalties .
this site contains information that is intended for residents of canada only . residents of the united states should consult the emd serono , inc . website at urltoken for information on products and services approved in the us .
life sciences industry , emd serono recently invested in expanding its research and development presence in the state to support the advancement of its pipeline and opportunities for partnerships in the academia and biotech sectors . today , the emd presence in
, president and ceo of the accelerated cure project for ms .
we are thrilled that emd serono , a leader in the area of ms therapeutics , has chosen to take a lead founding sponsor role , providing the support needed to implement this important study .
operate under the umbrella brand emd . around 39 , 000 employees work in 66 countries to improve the quality of life for patients , to further the success of customers and to help meet global challenges . the company generated total revenues of €11 . 1 billion in 2013 with its four divisions : biopharmaceuticals , consumer health , performance materials and life science tools . merck kgaa of darmstadt ,
you are now leaving the website of merck kgaa , darmstadt , germany’s biopharma business . this link may lead to a resource maintained by third parties over whom we have no control . as such , we are not responsible for and makes no representation as to the accuracy or any other aspect of such resource or the privacy practices of such third party . providing links to a third party website does not constitute an endorsement by our company of such website or the information or products presented on such website .
this site contains medical information that is intended for residents of the united states only and is not meant to substitute for the advice provided by a medical professional . always consult a physician if you have health concerns . use and access of this site is subject to the terms and conditions as set out in our legal statement and privacy policy . this site contains information that is intended for us residents only . canadian residents should consult the emd serono canada inc . website at urltoken for information on products and services approved in canada
html public
- / / w3c / / dtd xhtml 1 . 0 transitional / / en
urltoken
this site contains medical information that is intended for residents of the united states only and is not meant to substitute for the advice provided by a medical professional . always consult a physician if you have health concerns . use and access of this site is subject to the terms and conditions as set out in our legal statement and privacy policy .
html public
- / / w3c / / dtd xhtml 1 . 0 strict / / en
urltoken
as a user from north america , you are automatically forwarded to urltoken . please use our contact us page to get more information about our country - specific activities outside of north america .
accommodation for applicants with disabilities is available as part of the application and recruitment process . if you would like further information on accommodation , please contact hr at 855 - 444 - 5678 .
this website uses ' cookies ' to give you the best , most relevant experience . using this website means you’re ok with this . you can change which cookies are set at any time - and find out more about them in our cookie policy .
you have accessed urltoken , but for users from your part of the world , we originally designed the following web presence urltoken .
by sharing this content , you are consenting to share your data to this social media provider . more information are available in our privacy statement .
we are committed to delivering a positive experience for all of our patients . our momentum patient support team is available 24 / 7 in 250 languages , and . . . more
we are committed to delivering a positive experience for all of our patients . our momentum patient support team is available 24 / 7 in 250 languages , and includes field nurses who are part of a patient’s extended healthcare team offering training and other support services in the home and in a community setting .
we help people better understand and manage their disease through relevant and user - friendly education resources and a dedicated patient support team .
to learn more about the company ' s business outside of canada , please visit the emd group website .
html public
- / / w3c / / dtd html 4 . 01 transitional / / en
urltoken
as we continue to set ambitious goals , we have learned the importance of collaboration . so , we’ve created many ways for innovators like yourself to join us in making a difference in the world .
over our long history we’ve developed the reputation , expertise and infrastructure to do cutting - edge internal scientific research and product development . however , to best serve our customers and meet our goal of changing the world , we also think it’s vital we partner and collaborate with others , beyond our own laboratories . we are committed to broadening our relationships with other innovators , scientists and entrepreneurs in a variety of ways , based on your needs and objectives . our goal is to find a way to match our resources with your initiatives and help you maximize their potential .
“to us , creating an effective partnership means to combine our strengths with those of our partner to unlock the knowledge and insights of both partners .
if you’re looking for a resolute partner with a proven track record as transparent , reliable and an industry leader , we want to hear from you about what you’re working on .
our corporate venture fund can help you go that extra mile . we’ve dedicated resources and employees to target and support young companies with great ideas for new products or technologies . is yours next ?
our accelerator was designed to help innovative start - ups take off with three months of financial support , office space and access to our network of international experts .
the research agreement will build on a collaboration established in 2004 and will extend for two more years to develop pre - clinical and clinical research projects using a translational approach . the partners will target serious and debilitating neurological diseases that affect young adults , such as multiple sclerosis .
professor of the department of neurology at san raffaele hospital , and inspe director professor giancarlo comi , said that public and private institutes’ partnership with pharmaceutical companies bring much needed funding to research projects . “in compliance with the respective prerogatives and role of research institutions and companies in the pharmaceutical market , these forms of collaboration allow research institutes to actively participate as real drivers at the development of new therapies and at the definition of biomarkers , as essential tools for the drugs optimization . ”
copyright © 1996 - 2018 vertmarkets , inc . all rights reserved . terms of use . privacy statement . subscriber request form .
with the biorn guide you gain access to an information platform on life sciences in the biotech cluster rhine - neckar in germany . find biotechnology companies and renowned research institutes in europe ' s hottest spot for personalized medicine and cancer research . all biotech organizations located in the biorn cluster are listed with a basic address . biorn network members have the opportunity to fill in an extended company profile .
and the accelerated cure project for multiple sclerosis today announced a lead founding sponsor agreement to help launch the optimizing treatment—understanding progression ( opt - up ) study .
opt - up is a u . s . - based , multicenter longitudinal clinical research study that will enroll 2500 people with ms and follow them for up to five years . the goals of the study are to generate a robust evidence base of factors affecting treatment outcomes in ms to guide the choice of treatments and other interventions for ms patients , and to produce knowledge and tools for developing strategies and / or medicines to slow , arrest , or reverse ms progression .
our collaboration with the accelerated cure project on the opt - up clinical research study offers us an extraordinary opportunity to combine complementary expertise and resources to improve patient outcomes ,
said dr .
.
this study underscores our company ' s dedication to furthering breakthrough scientific research that can advance treatment options for those living with multiple sclerosis .
subjects will be enrolled at up to twenty ms clinics located throughout the u . s . and will be followed for a minimum of two years and up to five years . using validated and standardized instruments , researchers will collect high - quality data on treatment outcomes , biological samples , and imaging data that will be analyzed by the acp network investigators and partner organizations , as well as shared widely with research groups that can help accomplish the goals of opt - up .
and chair of the opt - up steering committee .
the opt - up study objective is to provide data and insights to better match people living with ms with the treatments .
southwestern .
i believe that the substantial amount of data and biosamples generated by this study will be enormously valuable in furthering our understanding of ms disease progression .
about accelerated cure project for ms accelerated cure project for ms ( acp ) is a nonprofit organization whose mission is to accelerate research efforts to improve diagnosis , to optimize treatment and to cure ms . acp believes that research is the only way to greatly improve the outlook for people with ms . the organization promotes scientific collaboration and accelerates research by rapidly and cost - effectively providing researchers with data and biospecimens they need to explore novel research ideas that can lead to better diagnoses , to new treatments and to cures for people with ms . its resources have supported 77 research studies worldwide that have generated almost 700 million returned data points for collaborative data mining and disease modeling . to learn more about the activities , and impact of acp , please visit urltoken .
, is a leading us biopharmaceutical company focused exclusively on specialty care . an established leader in the
, is a leading company for innovative and top - quality high - tech products in the pharmaceutical and chemical sectors . its subsidiaries in
is the world ' s oldest pharmaceutical and chemical company – since 1668 , the name has stood for innovation , business success and responsible entrepreneurship . holding an approximately 70 percent interest , the founding family remains the majority owner of the company to this day .
about multiple sclerosis multiple sclerosis ( ms ) is a chronic , inflammatory condition of the central nervous system and is the most common , non - traumatic , disabling neurological disease in young adults . it is estimated that approximately two million people have ms worldwide . while symptoms can vary , the most common symptoms of ms include blurred vision , numbness or tingling in the limbs and problems with strength and coordination . the relapsing forms of ms are the most common .
warning : the ncbi web site requires javascript to function . more . . .
robert j . fox , mellen center for multiple sclerosis , neurological institute , and lerner college of medicine , cleveland clinic , 9500 euclid ave , u - 10 , cleveland clinic , cleveland , oh , 44122 usa . email : gro . fcc @ rxof
received 2011 jun 29 ; revised 2012 jul 18 ; accepted 2012 jul 22 .
this is an open - access article distributed under the terms of the creative commons attribution license , which permits unrestricted use , distribution , and reproduction in any medium , provided the original work is properly cited .
despite significant progress in the development of therapies for relapsing ms , progressive ms remains comparatively disappointing . our objective , in this paper , is to review the current challenges in developing therapies for progressive ms and identify key priority areas for research . a collaborative was convened by volunteer and staff leaders from several ms societies with the mission to expedite the development of effective disease - modifying and symptom management therapies for progressive forms of multiple sclerosis . through a series of scientific and strategic planning meetings , the collaborative identified and developed new perspectives on five key priority areas for research : experimental models , identification and validation of targets and repurposing opportunities , proof - of - concept clinical trial strategies , clinical outcome measures , and symptom management and rehabilitation . our conclusions , tackling the impediments in developing therapies for progressive ms will require an integrated , multi - disciplinary approach to enable effective translation of research into therapies for progressive ms . engagement of the ms research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease - modifying and symptom - relief treatments for progressive ms .
the last two decades have seen dramatic progress in relapsing–remitting multiple sclerosis ( rrms ) . experimental autoimmune encephalomyelitis ( eae ) and other animal models have provided insights into the pathophysiology of central nervous system inflammation and demyelination . clinical diagnostic criteria have been refined , and biomarkers are being developed that predict future disease activity and disability . a clear pathway has emerged for developing rrms therapies : studies in experimental models , phase i safety studies , phase ii trials with active mri lesions as the primary outcome , and finally phase iii trials using relapses and sustained progression of disability as primary outcome . eight disease - modifying therapies have received regulatory approval for rrms and several more are in late - stage clinical development and could receive regulatory approval shortly .
for all the success in developing treatments for rrms , the story in progressive ms is comparatively disappointing and more challenging . even the definition of progressive ms has been elusive . at the clinical level , progressive ms is defined as the gradual progression of clinical disability in a patient either with a preceding relapsing course ( secondary progressive ms , spms ) or without a preceding relapsing course ( primary progressive ms , ppms ) . 1 there may be superimposed evidence of overt inflammation , but frequent relapses and many new lesions on mri are more suggestive of rrms . at the imaging level , progressive ms is the gradual accumulation of imaging abnormalities . at the pathology level , progressive ms is the abnormal processes present in neurons or glial cells that lead to irreversible injury that causes clinical disability progression . an inherent difficulty in studying progressive ms is the indistinct overlap with rrms , with the pathologic origins of progressive ms probably developing much earlier than its clinical manifestations . here , ppms and spms are grouped together , since they share many similarities – clinically , pathologically , and particularly as revealed by imaging technology . 2
animal models such as eae provide only limited insight into the pathophysiology of progressive ms . new mri lesions are only occasionally seen in progressive ms , resulting in uncertainty as to which imaging or other biomarker should be employed in phase ii proof - of - concept clinical trials . the clinical metrics used in rrms have unclear sensitivity in progressive ms , limiting their utility . mechanisms for identifying candidate therapies among existing therapies are not well defined .
clinical trials of anti - inflammatory therapies in progressive ms have been generally negative or inconsistent . immunosuppressive and immunomodulating drugs such as cladribine , azathioprine , and cyclophosphamide have shown no evidence for efficacy in spms and ppms . only mitoxantrone has been approved for spms in some countries , and this treatment has a serious adverse effect profile . finally , early attempts to approach progressive ms with putative neuroprotective therapies have failed , as seen in the recent trial of lamotrigine . 3
given the challenges presented by progressive ms , a collaborative was convened by volunteer and staff leaders from several ms societies ‘to expedite the development of effective disease - modifying and symptom management therapies for progressive forms of multiple sclerosis’ . through a series of scientific and strategic planning meetings , five key priority areas for research were identified (
) . these areas represent opportunities where concerted research efforts would provide significant impact in overcoming the current barriers in developing effective treatments for progressive ms and provide a clear roadmap for the future .
experimental models for ms have provided important insights into disease pathogenesis and potential therapies . 4 neurotoxicity models inform neuroprotection strategies that may prevent neurodegeneration in ms . 4 the three most commonly studied animal models in ms are : eae , virally induced demyelinating disease models and toxin - induced models of demyelination . 5 despite their extensive use , the clinical course , immunology and neuropathology of these models reflect only part of the pathophysiological spectrum of human ms . 4 , 6 therefore , direct extrapolation of results obtained in these models to ms is often tenuous , and the effect of therapeutic interventions in animals must be interpreted with care . 7 in addition , most of the current models follow a monophasic episode of inflammation and therefore predominantly mirror only the impact of acute inflammation and neuronal injury seen in rrms . 4 , 6
several animal models claim to represent human progressive ms , 8 but few offer compelling evidence . 6 the chronicity of these models is usually short and the composition of lesions different from ms . 6 furthermore , most of these models do not reflect the irreversible deficits characterizing progressive ms . 9
therefore , there is an urgent need for better animal models that reproduce the key clinical and pathological features of spms and ppms . such models should include the role of cd8 - positive t cells and notably macrophages , which comprise a major component in progressive ms lesions . ectopic b cell follicles should be studied as an alternative disease - related mechanism . additional models are also needed that demonstrate robust chronic demyelination and neurodegeneration , such as an autoimmune - independent , inflammatory glial cell - associated neurodegeneration , which more accurately reflects progressive ms . in addition to animal models , brain - slice cultures that demonstrate demyelination and neurodegeneration may be informative , especially if they can be adapted to use human post - mortem tissue where ms pathology can be directly examined .
while our understanding of the pathophysiology of progressive ms is yielding knowledge which can be applied to the development of new treatments , identifying and validating targets for use in drug discovery for progressive ms remains a significant challenge . helpful insights may come from genome - wide association studies ( gwas ) . since the first non - mhc susceptibility locus ( il2ra ) was identified , 10 the list of ms risk loci is growing , with around 50 loci identified to date . 11 however , no individual gene variant has been identified as the ideal therapeutic target and , even when considering all disease - associated variants together , risk loci explain only a modest fraction of disease heritability . 12 notwithstanding these limitations , the available results may suffice for computational and systems biology analyses to provide novel insights into biological pathways involved in disease pathogenesis . indeed , computational biology is shifting from diagrammatic representation of pathways to mathematical models . these techniques hold promise to provide the tools for interpreting genetic data across different knowledge domains . 13 furthermore , systematic assessments of the functional consequences of the associated variants are underway . together , the results of these studies could help prioritize putative therapeutic targets and steer the development of new compounds .
in addition , methods have recently been developed to select old drugs for new targets . historically , repositioning of a compound for a new indication has been a chance occurrence , driven by observations of unforeseen favorable effects . now there is intense research on how to systematically infer new therapeutic targets for drugs that have already been registered for human use . side - effect or chemical similarities between drugs and ligand sets are examples of this new strategy . 14 , 15 these data may be further refined through screenings of registered drugs on cellular and animal models of ms .
superimposing biologically relevant pathways identified through gwas studies to ‘catalogues’ of phenotypic effects of registered drugs may shorten the process of identifying therapies with potential efficacy in progressive ms . this strategy is safe for patients , since repurposed drugs usually come with years of post - marketing experience in other diseases . this strategy is also cost - effective , since it streamlines preclinical and early - stage clinical studies . indeed , the latest gwas data did not show substantial differences at susceptibility loci between relapsing and primary progressive forms of ms , suggesting relevance of gwas results to progressive ms . 11
the therapeutic opportunities that come from gwas , computational biology and systematic reassessment of the effects of pharmaceutical compounds need further development to achieve their potential application to progressive ms . intellectual property and the possibility of re - evaluating compounds that have not made it through the approval process are among the issues that , if properly addressed , may help accelerate the development of effective therapies for progressive ms . 16
agents for which there is promising preclinical data need to be developed through early phase clinical trials for evidence of safety and therapeutic benefit . phase ii trials generally rely on biomarkers that are more sensitive to therapeutic effects than clinical measures . biomarker outcomes enable phase ii trials to be shorter and have a smaller sample size than phase iii trials .
valid surrogate biomarkers need to predict clinical outcomes . phase ii trials in rrms have advanced because lesion activity on mri is an accepted biomarker of clinical relapse rate . 17 in contrast , no comparable measure has been identified in progressive ms . there are no agreed imaging markers of neurodegenerative processes such as energy failure , ionic imbalances and loss of neuronal integrity . the problem is compounded by limitations of clinical measures of disease progression against which any biomarker might be validated .
at present , promising imaging metrics include cerebral and spinal cord atrophy , lesion t1 hypointensity , magnetization transfer ratio to assess lesion microstructure , and optical coherence tomography to measure axonal degeneration in the retina . 18 there is enough longitudinal data to enable sample sizes to be calculated for most of these techniques for proof - of - concept trials , but their sensitivity to change and responsiveness to treatment is not well understood . newer techniques that assess tissue microstructure are also candidate metrics , including diffusion tensor imaging 19 in addition to methods that can derive axonal density and radius . techniques that examine earlier events in the injury pathway include sodium imaging 20 and measurements of metabolic markers , including the neuronal / mitochondrial marker n - acetylaspartate . 21 these techniques could be complemented and extended by positron emission tomography ( pet ) . 22 little is known about the sensitivity , responsiveness and predictive power of most of these imaging techniques and their limited availability may restrict their widespread use .
a number of tissue fluid biomarkers have been studied , mostly to assess immunological activity . markers of specific injury mechanisms are also emerging , including chemokines associated with intrathecal b lymphocyte activity that might drive cortical injury , 23 nitric oxide metabolites , 24 and neurofilaments released by damaged axons . 25 a significant drawback to widespread application of these biomarkers is their typical measurement from cerebrospinal fluid , which is not easily accessible . nonetheless , cerebrospinal fluid is increasingly incorporated into designs of progressive ms trials , and efforts to identify biomarkers in plasma and serum are underway .
better biomarkers would power smaller and shorter trials . more flexible trial designs are also being examined to achieve the same aim . these include modified entry criteria to enrich trials for patients more likely to progress . adaptive designs such as those used in cancer trials could make use of prognostic biomarkers to stratify an outcome analysis that is sensitive to subpopulation treatment effects , 26 and could employ an interim futility analysis to exclude non - effective agents . 27
these considerations suggest that proof - of - concept clinical trial strategies are likely to evolve significantly if ( 1 ) biomarkers can be identified and validated that measure important events in the neuronal injury pathway , are reliable , easily implemented , dynamic over time , and correlate with disability , and ( 2 ) if trial designs can be developed which further minimize trial size and duration . importantly , these innovations will need sufficient community consensus to be accepted by regulatory authorities .
a critical aspect in the development of therapies is a measurement tool of therapeutic efficacy . the ideal measurement tool is precise , reproducible , broad - based in its assessment , sensitive to change over time , and predictive of future change . the evaluation of ms therapies in rrms was greatly assisted by clear definitions and objective measurement of clinical relapses . establishing outcome measures for progressive ms has been more difficult . this difficulty arises from the varied manifestations of progressive ms ( motor , sensory , coordination , cognitive , etc . ) , their slow rate of evolution , and difficulties in their quantitative measurement . there are two main pathways to solving this challenge : refinement of existing outcome measures and development of new outcome measures .
of the existing measures , the kurtzke expanded disability status scale ( edss ) 28 is the most common disability measure in ms trials . however , edss is an inherently subjective assessment by a neurologist , has poor intra - and inter - rater reliability , 29 and has poor precision . refinements to the edss would likely improve its performance , although many of its shortcomings are inherent to the tool and so are insurmountable .
the multiple sclerosis functional composite ( msfc ) is the outcome of an international panel charged with replacing the edss . 30 advantages to the msfc include its dynamic assessment of different functions relevant to ms ( ambulation , arm function , and cognition ) and improved statistical performance . since the introduction of the msfc , many validation studies have shown its clinical correlations and predictive capacity . despite these apparent advantages , the msfc has not always been more sensitive than the edss in clinical trials . equally important , the msfc has not yet been accepted by regulators as an alternative to edss . as with edss , further refinement of the msfc may improve its sensitivity , reliability , and responsiveness , although some shortcomings cannot be overcome . 31
important goals of ms therapies are to reduce symptom severity , improve function , and enhance quality of life . these are best evaluated through patient - reported outcome measures ( proms ) , including global assessments of daily function and health - related quality of life ( hrql ) measures . 32 regulatory interest in proms is growing , with guidelines emerging regarding the integration of proms into clinical trials . 33 efforts to improve clinical disability assessment in ms are already underway . 31
ms results in a diversity of symptoms , bringing increasing physical , psychological and emotional burden , particularly in the progressive stage of the condition . in spite of the introduction of effective disease - modifying treatments , symptom management and rehabilitation remain essential components of ms therapy , helping to alleviate the impact of disability and improve quality of life . surprisingly , the rationale for specific pharmacological treatments for symptoms is frequently based on few trials with small patient numbers , often underpowered and unblinded . 34 recently , these shortcomings have begun to be addressed with a few well conducted studies , such as using cannabinoids 35 and fampridine 36 for motor symptoms . while cognitive deficits can now be clearly defined , fatigue remains more difficult to evaluate in trials because ( a ) less is known about the pathophysiology and ( b ) it may be influenced by psychiatric factors , making quantitative characterization problematic and often confounded . depression and anxiety may respond well to either pharmacologic or cognitive behavioral treatment . 37 – 39 symptom management in ms can be advanced in a number of ways . first , there should be targeted research to improve our understanding of the pathological mechanisms leading to symptom - related disability . this knowledge will allow more focused translational steps towards developing symptomatic therapies . secondly , potential treatments should be assessed in rigorous , well designed trials that are sufficiently powered to establish beneficial effects , the optimum dosage , and short - and long - term side effects . potential symptom interactions and confounding factors should be accounted for in the trial design . ideally , studies should incorporate proms , surrogate pathological markers related to the particular symptom under study and an assessment of cost - effectiveness . third , further development of reproducible and responsive measures for different symptoms is needed .
symptomatic treatment is normally part of a multidisciplinary patient - centered approach that may involve rehabilitation . the relationship between neuroplasticity and rehabilitation is a critically important area for further research . functional brain reorganization is well described in ms , showing increasing activation extent and the recruitment of additional areas , and hinting at the prospect of compensatory strategies . 40 , 41 some motor networks may be altered by training 42 but there is a need to investigate if enhancing network plasticity may improve the outcomes of rehabilitation . combining functional and structural imaging with cognitive rehabilitation may help develop treatments for cognitive impairment . 43 finally , applying brain–computer interface technology in patients with advanced ms may allow greater motor independence , communication and environmental control . 44
despite great progress in relapsing ms , much work is needed to achieve similar successes for progressive ms . there are a number of key areas of unmet need which are blocking treatment development in progressive ms . although the international scientific community has made progress in some of these areas (
) , there have not been commensurate gains in progressive ms treatments . tackling these issues will require an integrated , multi - disciplinary approach to enable effective translation of research into therapies . to this end , the international progressive ms collaborative is committed to engaging the ms research community through an international effort to fund a spectrum of research activities relevant to progressive ms with the ultimate goal of expediting the development of disease - modifying and symptom - relief treatments for progressive ms .
to address these five challenging areas , which currently impede the treatment of progressive ms , the international progressive ms collaborative commissioned five working groups , comprised of international experts , to identify specific strategies and potential lines of research that would overcome the barriers and realize the opportunities within each area . following an international meeting in early 2013 , we anticipate that a call will be issued to address these opportunities . potential sources of funding for this call include the existing research funding mechanisms of the member organizations of the international progressive ms collaborative as well as other partners ( e . g . , government , industry ) . in addition , there will be an international fundraising effort led by the multiple sclerosis international federation and financial support will be solicited from diverse channels around the world , including foundations , government , corporate , and private funding organizations .
fostering global collaboration by the ms research community is a bold ambition , and potentially fraught with many challenges . fortunately , the opportunities have never been as favorable as they are today , with unprecedented data on disease etiology , pathophysiology , and disease course . furthermore , we can look to other diseases for inspiration . collaborative efforts like the forum for collaborative hiv research , the alzheimer’s disease neuroimaging initiative , and the innovative medicines initiative , provide powerful examples of how collaboration can accelerate research among a diverse group of stakeholders . while the collaborative efforts in progressive ms will almost certainly differ from those in other fields , the time is right for concerted action .
the meetings of the international collaborative on progressive multiple sclerosis were funded by the italian multiple sclerosis foundation ( fism ) , ms society of canada , ms international federation , ms research foundation ( the netherlands ) , uk ms society , and the national ms society ( usa ) .
funding : this activity received no specific grant from any funding agency in the public , commercial , or not - for - profit sectors .
conflict of interest : robert j . fox received personal compensation for activities with avanir , biogen idec , novartis , and questcor , and research support from the national ms society ( usa ) and national institutes of health ( usa ) .
david baker is a founder of canbex and has received personal compensation for activities with ucb and biogen idec .
olga ciccarelli is on the editorial board of neurology and is a clinical editor for cml multiple sclerosis . she has received research funding from the wellcome trust , ms society of great britain and northern ireland , ucl biomedical research centre , and engineering and physical sciences research council . she has received speaker honoraria from bayer - schering and ge healthcare .
antel j , antel s , caramanos z , arnold d , kuhlmann t .
denic a , johnson aj , bieber aj , warrington ae , rodriguez m , pirko i .
campillos m , kuhn m , gavin ac , jensen lj , bork p .
sormani mp , bonzano l , roccatagliata l , cutter gr , mancardi gl , bruzzi p .
paling d , golay x , wheeler - kingshott c , kapoor r , miller d .
noseworthy jh , vandervoort mk , wong cj , ebers gc . the canadian cooperative ms study group
trials obotiacoc and sclerosis im . disability outcome measures in multiple sclerosis clinical trials : current status and future prospects
mohr dc , boudewyn ac , goodkin de , bostrom a , epstein l .
kim sp , simeral jd , hochberg lr , donoghue jp , friehs gm , black mj .
* final gross price and currency may vary according to local vat and billing address . * your purchase entitles you to full access to the information contained in our drug profile at the time of purchase . a link to download a pdf version of the drug profile will be included in your email receipt . adis is an information provider . we do not sell or distribute the pharmaceutical compounds written about in this database .
orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases .
oops , it looks like you don’t have a valid subscription to this content . to gain full access to the content and functionality of the adisinsight database try one of the following .
if you are a subscriber to this content then contact us at asktheexpert . adisinsight @ urltoken so we can help .
in 2017 , domain therapeutics has incorporated seagull with three academic researchers from ircc ( torino university ) . the asset centric company is aiming at leading to the clinic a mutated version of the semaphorin 3a ( sgl 10060 ) abled to reprogram the tumor microenvironment ( tme ) . the tme is known to promote the tumorigenesis , to ease the dissemination of metastasis and offer an immunosuppressive context . in multiple in vivo models , sgl 10060 was shown to inhibit the release of metastasis , to potentiate the immune response and normalize the tumor vascularization . backed to a strong ip , the program is entering regulatory preclinical development .
in 2016 , domain therapeutics and medicxi , a swiss venture fund dedicated to financing asset - centric companies , created mavalon therapeutics , a company focused on stopping the progression of parkinson’s disease . mavalon therapeutics is developing the first orally available small molecule able to induce gdnf production within the brain of parkinson’s patients . gdnf is a naturally occurring factor promoting the growth of dopamine neurons . the drug candidate , a positive allosteric modulator of the metabotropic glutamate receptor type 3 ( mglur3 pam ) , was discovered and initially developed by domain therapeutics with the support of the michael j . fox foundation . medixci committed up to €9m ( $ 10m ) in mavalon .
press release : domain therapeutics ' business model validated : lundbeck acquires prexton therapeutics for $ 1 . 1b
in 2012 , domain and ono pharmaceutical co . , ltd . ( osaka - japan ) signed a collaboration agreement focused on discovering small molecules targeting g - protein coupled receptors ( gpcrs ) . under the agreement , ono will pay to domain therapeutics upfront payment , research funding for the collaborative research programs , success - based milestones on the research and development progress , as well as royalties on sales of the products . domain therapeutics will apply dtect - all™ , its proprietary gpcr drug discovery platform and its expertise in gpcr medicinal chemistry and pharmacology to design and optimize small molecules into drug candidates having activity against gpcrs selected by ono . ono will have worldwide exclusive rights to develop and commercialize any pharmaceutical product arising out of the drug discovery collaboration .
in 2008 , domain therapeutics signed a research agreement with takeda pharmaceutical company limited , japan ' s largest pharmaceutical company . under the agreement , domain therapeutics applied its dtect - all™ platform to identify novel drug candidates that target undisclosed g protein - coupled receptors ( gpcrs ) of interest to takeda . in 2009 domain therapeutics announced that it has successfully completed the first milestone in this research agreement with takeda pharmaceutical . following milestone completion have not been publicly announced .
sanofi and mit ' s center for biomedical innovation has established a new partnership to foster basic and applied research and develop solutions to address unmet clinical needs . sanofi will be providing f . . .
sanofi and stanford university ' s bio - x have entered into a multi - year collaboration that support interdisciplinary collaborative research to be conducted at stanford . a joint steering committee comprisi . . .
janssen pharmaceuticals ( formerly omjpi ) a johnson and johnson entity has entered into collaboration agreement with johns hopkins brain science institute (
bsi
) at johns hopkins university . janssen wi . . .
janssen pharmaceutical a division of johnson & johnson has entered into partnership with harvard university - evotec ' s diabetes program called curebeta . janssen will paying $ 300million in milestone paym . . .
cerecor a baltimore based company has taken an option with johns hopkins university to license d - amino acid oxidase inhibitors ( daao ) to treat schizophrenia . the daao inhibitor molecules are currently b . . .
gibh is a medical research institute affiliated with the chinese academy of sciences . cwhm has been collaborating with gibh scientists since 2010 on a project to discover and develop new medicines for mala . . .
cwhm signed a joint research agreement in 2010 with the institute for one world health to discover and develop new drugs to combat diarrhea , which is the second leading cause of death worldwide in children . . .
the mission of senex biotechnology is to discover and develop therapeutic agents to effectively treat cancer , viral diseases and age - related diseases , such as alzheimer ' s , renal disease , atherosclerosis , a . . .


myfonts is a digital fonts distributor , based in woburn , massachusetts .

it was created by bitstream inc. , launched in september 1999 ( during the atypi conference in boston ) , and started selling fonts in march 2000 .

in november 2011 monotype imaging announced plans to acquire myfonts and the other font-related parts of bitstream for $ 50 million in cash .

the acquisition was concluded in march 2012 .

myfonts

these are the top 50 selling fonts from all of myfonts in the last month . updated hourly !
the world’s largest collection of fonts for print , products & screens . looking for customer support ? email help @ myfonts . com .
myfonts was established in january 1999 as a division of bitstream inc . ( nasdaq : bits ) to create a n . . .
both myfonts and whatthefont are considered highly useful tools for designers and layout artists looking to purchase commercial fonts . the combination of monotype’s classic foundry styles , with myfonts more non - traditional and modern fonts should make for an attractive boost to the offerings available through the service .
hey , boston - area designers , typographic aficionados , and dribbble family members ! we’re excited to host a meetup of local design talent at our myfonts headquarters—come hang out with us for an evening of food , drink , and celebration of type and design .
tnw uses cookies to personalize content and ads to make our site easier for you to use . we do also share that information with third parties for advertising & analytics .
monotype imaging has announced plans to acquire urltoken and whatthefont , as well as other products of bitstream for $ 50 million cash .
will get in the deal will be the bitstream typeface library , as well as its font fusion and panorama font rendering and layout technologies . there are also 10 font - related patents included . about 15 of bitstreams employees and 40 engineers , based in the u . s . and india , respectively , will join monotype .
monotype is an imaging company that focuses largely on the distribution of text rendering and user interface tech to manufacturers of printers , tablets , tvs , ebook readers as well as publishers and corporations . bitstream is on the other end of the spectrum and , from its early life as a font foundry , grew to focus on the consumer aspects of fonts with urltoken and its font matching and discovery service whatthefont .
stay tuned with our weekly recap of what’s hot & cool by our ceo boris .
sit back and let the hottest tech news come to you by the magic of electronic mail .
prefer to get the news as it happens ? follow us on social media .
got two minutes to spare ? we ' d love to know a bit more about our readers . start !
over 130 , 000 available fonts , and counting . check out some of our latest releases…
these great deals are expiring soon , act now to save on these awesome fonts .
submit an image to whatthefont to find the closest matches in our database . or , let cloak - draped font enthusiasts lend a hand in the whatthefont forum
png , gif , or jpeg image files . maximum file size : 2mb . for best results , see the image submission tips
we install your fonts via the free skyfonts software , which runs in the background of your computer .
these are the top selling fonts released within the last 50 days . updated hourly !
we ' ve detected that javascript is disabled in your browser . would you like to proceed to legacy twitter ?
analysis of the 2018 font purchasing habits is in full swing . i ' ll be sharing facts as i go leading up to my presentation at
to provide you font identification on images as well ! ( beta ) . we also made some speed update and add a dark mode : )
today is the final day to take the font purchasing habits survey . share your thoughts about fonts , and get some free fonts for your time ! our
highlights we have liesel , an eight - font , hand - lettered family whose traditional design and layered detailing sets it apart from the crowd .
a casually , quickly drawn brush script , authenia has just the right amount of texture , meaning that it looks great at any size . mika melvas’ bestselling script duo will bring an authentic , laid back look to any design
as heroic as the name suggests , lian types’ heroe will save you time , energy and stress that can go into picking a super display face . as classy as it is versatile , this nine - font family runs the design gamut
twitter may be over capacity or experiencing a momentary hiccup . try again or visit twitter status for more information .
you can add location information to your tweets , such as your city or precise location , from the web and via third - party applications . you always have the option to delete your tweet location history . learn more
here ' s the url for this tweet . copy it to easily share with friends .
by embedding twitter content in your website or app , you are agreeing to the twitter developer agreement and developer policy .
not on twitter ? sign up , tune into the things you care about , and get updates as they happen .
this timeline is where you’ll spend most of your time , getting instant updates about what matters to you .
hover over the profile pic and click the following button to unfollow any account .
when you see a tweet you love , tap the heart — it lets the person who wrote it know you shared the love .
the fastest way to share someone else’s tweet with your followers is with a retweet . tap the icon to send it instantly .
add your thoughts about any tweet with a reply . find a topic you’re passionate about , and jump right in .
bonny is a family of decorative serif fonts , designed for display typography . the letterforms are very condensed . they also contain a lot of stroke - contrast . bonny’s thin strokes often terminate in flourishes ; these . . .
mika melvas’ newest brush script , fineday , is available with two sets of decorative uppercase , connecting and non - connecting lowercase letters , and a large character set to accommodate most central and eastern european languages .
i want ! and there are prints available , so brb . ( thanks to the very talented nicholas matej : urltoken
this is really good . i wish i knew the name of the artist .
we’ll have live screen printing demos where you can print your own souvenir poster , plus we’ll be hosting an uproariously competitive type quiz . prove your typographic might , all with a chance to win some pretty great design - themed prizes , including books , prints and , yes , even fonts !
all of this is free , and happening on thursday , may 25th from 6 : 30 - 10 : 00 pm at our greater boston office . there’s limited space available , so make sure you rsvp as soon as you can . we can’t wait to meet you !
the event is taking place in the office our parent company , monotype . we’re located in the unicorn park office complex right off of i - 93 in woburn . take the montvale ave exit to unicorn park drive ; we’re up the hill , on the left in building 600 . if you end up at the marriott , you’ve gone too far . we’ll have folks manning the front door to let you in . once you’re inside the building , the party’s up on the 3rd floor .
yourself , your appetite , as well as a healthy passion for type , design , and friendly conversation .
the real fun stuff won’t kick off until 7 : 00 pm - ish , so you’ve got time to get yourself here .
log in or sign up for eventbrite to save events you ' re interested in .


whereonearth was a company based in the united kingdom and was acquired by yahoo! oct 18 , 2005 .

technology company , that worked with hutchson and yahoo the company was founded in 1995 with a purpose of producing geocoding technology for partners .

in 1998 it acquired gdc , and gdc 's global geo-database , geoplanet .

in 2002 , the company was awarded a contract to deliver the underlying technology for hutchison 3g geo services .

in 2002 , the company spun off gdc in a management buyout , but retained geoplanet .

in 2003 the company again reorganized with a view of generating web technology for geolocation , named internetlocality , for the extraction of location information out of web content and web searches , which eventually led to the yahoo acquisition in 2005 for integration with yahoo! search marketing project panama .

the whereonearth internet toolset is partly available as part of the yahoo developer network .

whereonearth

according to rafat , whereonearth has has a limited deal with yahoo for five years .
whereonearth is a technology company that enables on - line ' local ' . the company ' s ' internet locality ' software suite is the combination of its patent pending technology and locations data that uniquely enables whereonearth to significantly improve the relevance of local searches and advertising . whereonearth ' s localisation technology is used by many companies to link locations to industry specific information in order to assist in making informed business decisions . customers include lastminute . com , hutchison 3g , yahoo ! , moreover , royal and sun alliance and many others . for more information on internet locality and its various applications for local search and advertising , visit www . whereonearth . com .
location , location , location isn’t just the catchphrase of estate agents but is also the basis of whereonearth . com’s l - sphere technology , which allows users to find local amenities or a specified destination and then produces a map showing how to get there .
with all signs pointing to increased growth in the online advertising and local search categories , digital envoy and whereonearth are committed to making automated local search a reality by combining their leading geographical databases to deliver a single solution aimed at disambiguating local search queries as well as enhancing local search and ad targeting on a global basis .
atlanta ( march 2 , 2005 ) - digital envoy , the leading provider of ip intelligence solutions , and whereonearth , the leading provider of localization technology in the form of software and data for local search and advertising , today announced a partnership that will transform and expedite the delivery of relevant local search and online advertising globally .
this partnership combines digital envoy ' s patented ip intelligence , which uncovers information about online users such as geographic location to the city - level worldwide based solely on user ip address , with whereonearth ' s patent - pending global locations technology . this innovative approach marries the power of digital envoy ' s online location data with whereonearth ' s physical location data . for example , advertisers can now select to target specific geographic regions in any part of the world defined by telephone area codes , postal codes , localities or administrative areas ( such as boroughs or counties ) for advertising . advertising is then delivered only to those users whose ip addresses match the chosen geographic region . this new depth in targeting brings offline techniques online , allowing advertisers and search providers to both increase the relevance of advertising and search results , as well as to create unique new local ad markets .
while both companies have offerings that , on their own , play a vital role in helping to deliver on the promise of local search , together we can provide a truly powerful solution that will significantly improve location - based search and advertising relevance and reach ,
said dev patel , ceo of whereonearth .
we look forward to working together to bring this tool to any online company looking to capitalize on this emerging space .
whereonearth ' s physical location data is the ultimate complement to our leading online location data , further strengthening our position as the de facto standard for online advertising and search applications ,
said rob friedman , executive vice president of corporate development for digital envoy .
this partnership allows our companies to deliver an unrivaled solution that will help make true , localized search a reality - sooner than later - by eliminating many of the issues associated with current local search efforts such as geographically irrelevant results and advertisements .
about cbs interactive | contact | jobs | advertise | privacy policy | cookie policy | ad choice | terms of use © cbs interactive inc . all rights reserved .
html public
- / / w3c / / dtd html 4 . 01 transitional / / en
urltoken
furthermore , this combined offering raises the bar for the industry in terms of local targeting by allowing online advertisers to geo - target ads with even greater depth based on area codes and postal codes worldwide .
digital envoy ' s netacuity is the leading ip intelligence solution and is used across a number of industry verticals by some of the world ' s largest networks , web sites and enterprises including aol , microsoft , cable & wireless , ask jeeves , walt disney internet group , doubleclick , infospace , symantec , network associates , digital river , urltoken and many others . the company ' s patented and patent - pending technology provides new intelligence about an ip address such as location , connection speed and domain name , enabling a deeper understanding of the online universe . for more information on ip intelligence and its various applications , visit www . digitalenvoy . net .
company | business units | news | contact us | signup | site map © , digital envoy . all rights reserved . privacy policy .
yahoo boss offers premium search and geo api services allowing you to build innovative technology applications quickly and efficiently . boss also offers sponsored search and search advertising so that you can monetize your innovative products
at yahoo , we’re always looking for ways to streamline and simplify products for our customers . with this focus in mind , we will discontinue the boss json search api , as well as the boss placefinder api and boss placespotter api , on march 31 , 2016 .
access to the boss apis will continue until march 31 , 2016 . moving forward , customers leveraging the boss json search api can instead use ypa , a javascript solution that provides algorithmic web results with search ads for publishers who manage their own search engine results pages ( serps ) . click here to apply or learn more about ypa , or if you are working with a yahoo partner manager , they can help you explore your options .
if you have any questions regarding boss please visit our faqs page here or you may click here to get in touch .
build and launch web - scale search products that utilize the entire search index with the help of search api .
build a search application with customizations unique to your site and make money with search advertising .
get a free search box with yahoo ' s powerful search assist feature for your website .
make your applications location - aware by converting street addresses or place names into geographic coordinates ( and vice versa ) .
make your applications location - aware by identifying places mentioned in text , and identifing unique identifiers ( woeids ) .
i am being charged for usage , but i’m unable to add , modify or delete a payment method . what do i do ?
i ' m unable to view or download my usage report . what do i do ?
boss search api , boss placefinder api , boss placespotter api and boss hosted search .
you have until march 31 , 2016 to continue using it as you do today . your boss apis will still be available until the earlier of when we turn off the apps on march 31st , or you delete your app before march 31st .
it is important to yahoo that we can support and provide excellent service to our customers without delays , and with quality search results . we therefore made a decision to streamline our search offerings and discontinue the boss json and geo apis . developers can continue to get algorithmic web results from yahoo via ypa , which is available now . ypa is a client - side javascript solution that provides search ads and algorithmic web results for publishers who manage their own search engine results pages ( serps ) . click here to apply now .
we are no longer accepting new sign - ups to our boss apis . click here to apply or learn more about ypa .
if you have questions regarding boss you may click here for assistance . if you have questions regarding ypa , learn more here .
while the yql table geo . places geocoding and reverse geocoding are not replacements for boss placefinder , the yql table may suffice for some customers who do not need street address resolution . yql table geo . places will continue to be supported for our external developers .
yes , for those using boss hosted search from urltoken this product is discontinuing also on march 31 , 2016 . ypa might be a good fit to offer search ads and algo results on your own serp .
yes , this is part of boss search api and is also discontinuing march 31 , 2016 . we look to make search box with search assist available soon on this yahoo developer network .
we look to make search box with search assist available soon on this yahoo developer network , however after 3 / 31 customers will need to make code changes for it to work . we’ll announce the changes to the service soon .
billing cycles will still remain in force until your usage from that period is paid for . if you have any questions about your billing you may click here for assistance .
if you have another credit card available in yahoo wallet , and you wish to change your boss api payment to an existing card on file , please contact customer support here , and they can take care of the change . however , we recommend all users to consider changing to ypa as soon as possible . enjoy free algorithimic web results with ypa ! apply now .
please contact customer support here and provide your app id and date range with your request . they will provide your usage report .
please contact customer support here and provide your app id and the new daily limit amount you want to change to .
javascript seems to be disabled in your browser . you must have javascript enabled in your browser to utilize the functionality of this website .
html public
- / / w3c / / dtd html 4 . 01 transitional / / en
urltoken
( r - 69 ) real specimens gem gemstone mineral identification i . d . id chart rock
sellers have the right to set their own prices independently , but some manufacturers place restrictions on how these prices will be displayed or communicated to others .
copyright © 1995 - 2018 ebay inc . all rights reserved . accessibility , user agreement , privacy , cookies and adchoice
above is our well - known huge dragon turtle carving (
mr . turtle
) from china , carved within a single boulder and still attached ( with heidi beside it to show his size ) . the carving is 650 pounds , and is the first thing people see when they step inside our door .
you are about to embark on a 318 page shopping journey of weird , lovely and dead stuff , from cameos to woolly mammoth hair , ivory , teeth & bones , from shark & alligator teeth , gator feet & backscratchers to opals , eskimo ivory carvings & artifacts to maori fish hook necklaces , music instrument jewelry , dichroic glass , fairy stone crosses , titanium and amber jewelry , from alien stuff to rocks & meteorites , from prehistoric doo - doo to snake bite boxes , to hundreds of carvings of animals & gemstone skulls ; fossils galore . . . fasten your seat belt , and prepare for a journey to all continents and eras . . .
we believe we have created a website with a heart . any questions or problems whatsoever , pick up the phone & call us at : 864 - 541 - 8448 , or email us : whatnext1020 @ urltoken
we answer every single inquiry we receive via email , usually within 48 hours . so if you have not received a response , check your deleted file where your spam blocker may have put our response . or phone us or email us again , as your email may have been lost in cyberspace .
~ when you call us , you don ' t get a know - nothing clerk on the phone - you get heidi or glenn - owners of the business - right here in the usa . we can answer any of your questions about the products .
heidi or glenn takes your order , heidi ships it . no one else . are we flat - out busy ? yes ! we are huge where it counts - in inventory - and personal where it counts - in dealing with you .
~ you get what you see in the photo - no surprises . most items are individually photographed , removed from the site or marked sold when bought . stock items showing a single photo are clearly marked .
~ we own the stuff , it is right here , so we can physically look at it to answer your questions . no drop - shipping from a remote location .
~ buyer ' s bill of rights - shipping 100 - 300 packages a week , mistakes will happen . so when we error , we will make it right , whatever it takes .
~ security - we don ' t use your address or email address for anything except to ship your order & notify you . no spam emails or unsolicited mail . ever .
returns - our golden rule is : 100 % satisfaction on all your purchases . no excuse is needed to return the item within 7 days of purchase . insured returns suggested . all we ask is that you notify us that you are sending it back , and do so within the timeframe mentioned .
in an offline world 80 - 90 % of purchases happen within 8 - 10 miles of your home . we believe this will carry over into the online world and in an increasingly personalized internet , users should expect their search results to reflect their lives more precisely . same for advertisers ? they need to target users with more meaningful , relevant ads based on the user ? s locality .
sounds similar to my scenario with google being able to offer very localized advertising with their wi - fi ventures . john battelle makes a few interesting points about yahoo’s potential wi - fi plans on his blog .
as voice becomes dominant in search , and users turn to social media , apps and news aggregators for their content – and not to mention the rise in virtual reality – kevin gibbons asks whether we will still need websites in future .
one of the best ways to stay up - to - date with seo and search marketing developments is to keep a close eye on google ' s developments . however , just doing that can be a full - time job . luke budka highlights four recent updates you may not be aware of .
here are 12 alternatives to escape your reliance on google for all things search in 2018 .
as an seo , it ' s likely that you heavily rely on a number of time - saving tools . in this article , adam clemence shares the chrome extensions he can ' t live without .
say goodbye to google with these 14 alternative search engines , covering everything from information , images , videos , facts and stats . oh and gifs .
competitor monitoring informs content marketing strategy , inspires more content marketing tactics and helps you prevent content marketing mistakes .
when it comes to being visible online , video content is increasingly proving its worth as a way to grab attention and – crucially – to engage meaningfully with internet users . luke richards takes a look at the rise of video , alternatives to youtube , social and what it all means for search marketers .
github is home to over 28 million developers working together to host and review code , manage projects , and build software together .
if nothing happens , download the github extension for visual studio and try again .
where on earth ( woe ) data for timezones smushed up with eric muller ' s tz _ world _ mp shapefile for timezones . that ' s fancy talk for
polygons
.
this is an active but still experimental project to create a community - driven project to maintain and update the creative commons licensed geoplanet dataset .
rather than create a single repository with every record the plan is to create smaller datasets organized by placetype in the hopes that they will be more manageable to download and to update by users interested in particular place types .
each location ( timezone ) is stored as a separate geojson file . geojson was chosen because it has wide support in variety of gis tools , most programming languages ( and specifically javascript ) , can be edited using any old text editor ( or github ' s own
edit this page
functionality ) and allows for any number of custom key / value pairs using the geojson properties dictionary .
the naming convention for records is the timezone ' s where on earth ( woe ) id followed by a
. json
extension . records are stored in nested directories that correspond to their woe id . the top level directory would be the first three digits of a woe id , the second level directory would be the following three digits ( four through six ) and so on until their are no more digits in the woe id .
this repository includes countries from geoplanet ( versions 7 . 3 through 7 . 6 ) as compiled by woedb .
in the long - run github may not be the best venue for managing all of these records . but it ' s not an entirely crazy idea either so we ' re going to try it for a while because it ' s easy and safe .
you signed in with another tab or window . reload to refresh your session .
you signed out in another tab or window . reload to refresh your session .
founded in 1995 by steve packard , whose first company produced the trivial pursuit board game , urltoken supplies its services to risk assessors in the insurance industry and to internet search - engine providers such as yahoo . however , packard believes l - sphere’s main application will be in the third - generation ( 3g ) mobile telecommunications market . sales at the london company have grown 210 % a year from £265 , 000 in 1999 to £2 . 5m in 2001 , when it made big losses . the firm has raised £5m in venture capital from amadeus and reuters greenhouse among others .
this profile reflects the company at time of publication and does not reflect any changes that may have subsequently occurred . fast track and its sponsors do not endorse , guarantee or recommend investment in any of the companies .
for inquiries related to this message please contact support . for sales inquiries , please visit urltoken
if you believe this to be in error , please confirm below that you are not a robot by clicking
i ' m not a robot
below .
please make sure your browser supports javascript and cookies and that you are not blocking them from loading . for more information you can review the terms of service and cookie policy .