这个任务要求提供一种测试方法，能够简单的检测出血友病A 中凝血因子Ⅷ和血友病B 中凝血因子IX在血液中的水平。因为现在市面上所使用的测试方法都不太方便，都不适用于诊所，而且患者也不能在家里进行自我检测。这个任务要求提供一个半定量的测试方式，需要提供可靠的血液中凝血因子水平的资料，然后根据情况分为正常，轻微，严重三种疾病状态。 　　“征稿件请直接上传网址：https://www.innocentive.com” 　　TAGS: Engineering/Design, Chemistry, Global Health, Nature, Life Sciences, Food/Agriculture, Theoretical-IP Transfer 　　AWARD: $25,000 USD | DEADLINE: 2/21/13 | ACTIVE SOLVERS: 27 | POSTED: 12/21/12 　　The Seeker requires a test that could easily be used to monitor the level of blood coagulation factors FVIII or FIX present in hemophilia A and B patients, respectively. Today, many tests are commercially available, but none are suited for convenient testing either by care providers in the clinic or by hemophilia patients at home. A semi-quantitative test is required that would provide reliable information on the blood levels of FVIII or FIX relative to a state considered as ‘Normal’, ‘Mild’ or ‘Severe’ state of disease. 　　This Challenge requires only a written proposal. 　　Detailed Description & Requirements 　　Background 　　Hemophilia A and B are inherited coagulation diseases that severely impact the quality of life of persons afflicted. Hemophilia A is caused by lack of coagulation factor VIII (FVIII), while in hemophilia B patients lack coagulation factor IX (FIX). Although the diseases are to a large extent manageable using clotting factor supplement therapies, FVIII and FIX treatment needs to be monitored in order to ensure that it meets the requirements of the individual patients’ plasma level of the coagulations factor to be supplemented. Current tests require tedious laboratory analysis, not allowing patients to achieve the frequency of testing that would facilitate good management of their disease. 　　The Problem 　　Hemophilia patients are expected to benefit from daily monitoring of their disease status (i.e. measurements of FVIII or FIX levels) to check the efficacy of their therapy and the current status of their disease. Measuring clotting factors in the patient’s blood is currently the best way to assess hemophilia disease status. Current practice, i.e. taking a blood sample by phlebotomy requires health care workers assistance and cannot be done by the patients themselves. For future home measurement or point of care (POC) tests, novel tests allowing minimally invasive sample collection is required, e.g. finger prick tests to collect low-volume peripheral blood samples. 　　Today, a large number of tests are commercially available for laboratory testing of Factor VIII and IX in plasma – most of which are based on the capability of the test sample to form a clot or produce a color development following cleavage of a chromogenic substrate. Another principle entails binding of a specific antibody to the clotting factor followed by quantitative detection of the clotting factor-antibody complex. These methods are briefly described below, along with their limitations for home testing or POC testing: 　　Clotting Assay–This method measures the coagulation status of a patient’s plasma sample and compares it to a standard curve. In this assay, coagulation is initiated and clotting is assessed by kinetics measurements of turbidity. This method requires plasma preparation and specialized laboratory equipment. 　　Enzyme Linked Immunosorbent Assays (ELISA)– This test requires a cell-free sample (serum or plasma) of the patient’s blood. Multiple incubations and washing steps are required under laboratory conditions. Specialized bench-top colorimeters or luminometers are used to read the signal generated in each well of the immunoassay plate, and these readings are compared to a standard curve. 　　Bead-based Immunoassay -A number of liquid-phase technologies enable quantitative detection of multiple protein analytes based on their binding to specific antibodies linked to fluorescent beads. The patient samples are compared to a standard curve. Generally, these require expensive specialized equipment and multiple sample processing steps, including preparation of cell-free sample (serum or plasma). 　　Chromogenic assay -This assay requires plasma. After mixing the patient sample with different reagents, the formation of an active component of the coagulation process is measured by its capability cleave a chromogenic substrate. The color development is the read-out and it is correlated to a standard curve. The test is performed in microtiter plates. 　　The Seeker envisages a test that could be used either by a health-care-professional (HCP) and/or by the patient - this means that ease of use and robustness must be high and no skilled sample preparation must be needed. The test should give a semi-quantitative result within minutes, and the result needs to be interpreted either by the naked eye or by a hand held device, e.g. a small colorimeter, luminometer or a smart phone. 　　As with any diagnostic test, false positive and false negative rates must be low. Home or POC tests may not be carried out with the same level of standardization as laboratory tests, so tests that are amenable to internal positive and negative controls are required. 　　Proposed assay technologies should fulfill the following Technical Requirements. 　　The assay technology should: 　　Enable semi-quantitative analysis of FVIII or FIX in human blood sample so that the following disease status can be discriminated at a high level of accuracy: 　　Severe disease = <1% of ‘normal ‘plasma concentration 　　Mild disease = 1-5% ‘normal ‘plasmas concentration 　　Moderate disease = 5-40% = ‘normal ‘plasma concentration 　　FVIII ‘normal ‘plasma concentration = 100 ng/ml (0.3 nM) 　　FIX ‘normal ‘plasma concentration = 5 ug/ml (90 nM) 　　Be amenable to a high degree of standardization 　　Be easy to use at point-of-care for health care professionals and should not require specialist laboratory skills or equipment 　　Be highly specific i.e. not be influenced by ‘normal’ variations in human blood composition or cross reacting material. 　　Be amenable to mid-large scale production (>5 million/year) as a consumer diagnostic for home use 　　The proposed assay should not require: 　　Specialized laboratory instruments 　　Specialist analytical knowledge or laboratory techniques 　　Complex sample preparation of serum or plasma 　　Blood samples of more than >100 microliter volume (finger-prick volume) 　　Intravenous sampling or tissue biopsy 　　Any read out instrumentation, if required, should be hand held e.g. a small luminometer, smartphone or similar sized device 　　The Seeker considers the following requirements as ‘nice to have: 　　Self-test for home treatment e.g. dipstick 　　Low carbon footprint 　　Project Criteria 　　This is a Theoretical Challenge that requires only a written proposal to be submitted. 　　The submitted proposal should include the following: 　　The detailed description of the proposed Solution addressing specific Solution Requirements presented in the Detailed Description of the Challenge. 　　Rationale as to why the Solver believes that the proposed Solution will work as presented. This rationale should be supported with relevant examples and literature/patent citations. 　　Calculations, reference to existing data or literature that supports your claims for the assay technology – this need not be specific to the sample matrix and analytes described in the challenge, but should give the Seeker detailed insights into the potential of the proposed technology. 　　Diagrams illustrating the mode of action of the proposed assay technology and its use, if applicable. 　　Explanation of the proposed read out mode and commercially available devices (if required) that would fulfill requirements. 　　Calculations and justification of the lower limit of detection (LLOD) and resolution of testing – any precedence for technology 　　Insights into the limitations of proposed technology 　　An overview of how the proposed test would need to be developed to comply with 510k IVDD, including a brief risk analysis 　　Description of Solver’s expertise & resources relevant to the proposed technology 　　Your willingness, in principle, to form a collaborative relationship with the Seeker. 　　The proposal should not include any personal identifying information (name, username, company, address, phone, email, personal website, resume, etc.) 　　The Challenge award will be contingent upon theoretical evaluation of the proposal by the Seeker. 　　To receive an award, the Solvers will have to transfer to the Seeker their exclusive Intellectual Property (IP) rights to the solution. However, the Seeker will be willing to consider a licensingagreement for a partial award if exclusive IP cannot be transferred by the Solver.

一家世界500强的公司正在寻找一个或者多个的合作伙伴，共同开发天然除草剂，任何来源的都可以。这个任务其实很容易理解，因为现在只有相对较少的天然除草剂可消灭杂草或者其他物种，但是这些正在使用的除草剂如果在错误的条件下应用的话可能是有害的。 这是一项寻找合作伙伴的任务，投标者(包括团队或公司)只需要提交一份书面说明书，让公司进行评估是否建立合作关系，投标者需要提出一种新的化学方法或者尚未探讨过但是可能已有特定方式的新途径，新来源。 征稿件请直接上传网址：https://www.innocentive.com” Partner to Develop a Natural Herbicide TAGS: Life Sciences, Food/Agriculture, Chemistry, Requests for Partners and Suppliers, eRFP AWARD: varies | DEADLINE: 1/05/13 | ACTIVE SOLVERS: 4 | POSTED: 11/21/12 The Seeker, a Fortune 500 company, is looking for one or more collaboration partners to help identify and develop naturally occurring herbicides from any and all sources. It is well understood by this Seeker that there are relatively few natural herbicides for eradication of weeds or other invasive plants species and that those that are used today can be harmful if applied under the wrong conditions. This is an electronic Request-for-Partners (eRFP) Challenge; the Solver (including a team or company) will only need to submit a written proposal to be evaluated by the Seeker with a goal of establishing a collaborative partnership. The Solver should propose a novel chemistry or approach or novel source of naturally occurring herbicides that have not been previously explored but may have shown promise in an ad hoc way. Detailed Description & Requirements Background There are a number of natural pesticides available for insect control, but relatively few natural herbicides for the eradication of weeds or other invasive plants. Many of the recognized natural or non-synthetic phytotoxins that do exist can do more harm than good if they are applied under the wrong conditions, e.g., concentrated acetic acid, chelated iron, pelargonic acid, sodium chloride, or other concentrated chloride salts can be toxic to human health during mixing or application. Some plants may act as natural herbicides by emitting specific chemicals that cause injury or death to other plants growing nearby. Some well known examples include black walnut, sunflowers, sagebrush, and spotted knapweed. The process of certain plants acting in this way is called allelopathy. Researchers are very interested in the allelopathic qualities of plants, since the chemicals responsible for natural herbicides can often be isolated and refined for commercial use. It is well known that some naturally derived oils, such as cinnamon oil or clove oil, can cause phytotoxic effects and therefore serve the role of natural herbicide when liberally applied to some plant species. Another popular species of a natural herbicide can be found with the black walnut tree. The oils extracted from the leaves of this and other similar trees can be concentrated and often used in commercially produced herbicides. Extracts of chemicals found in sunflowers have reportedly been used by gardeners working “organically,” and these types of extracts may provide an important avenue to discovery of a whole new category of compounds of interest. Classically, there are two different means of recognized action from natural herbicides: Post-emergent herbicidesthat usually are applied to the leaves or roots of a plant after germination has occurred. Many of the natural herbicides described above are considered post-emergent. Pre-emergent herbicidesthat destroy other plants at the germination stage, before the plant can establish roots. Examples of natural pre-emergent herbicides are few with the example of corn gluten meal, an extract from corn syrup production, that disrupts the cell membranes only killing the tissue that it contacts. However, this Seeker is open to novel thinking that could be a radical shift in strategy, concept or approach. They are specifically interested in chemical compounds or microorganisms, however, so grazing animal species, mechanical, or thermal means of weed control will not be considered unique thinking. In addition, natural herbicides are often split into two categories based on their phytotoxic selecitivity: Selective herbicidesdo not severely damage the surrounding and “preferred” plants. An example of a natural selective herbicide may be found with the usage of fatty acids (soaps) to control dicot broadleaves or undesirable monocot grasses while not causing serious injury to the more common surrounding turfgrass found in yards or golf courses. Non-selective herbicidespromote injury nondiscriminately to all plants (monocots and dicots) in which there is physical contact. THE CHALLENGE The Seeker is looking for a collaboration partner to help identify and develop naturally derived products that would control pre-emergent dicot and monocot weeds. The action may be either selective or non-selective herbicide control but the preference is for selective control in both cool and /or warm season monocot turf grasses. The solution should not be based on a macro-organism (selective grazers), or a mechanical or thermal weed control option. While the Seeker will entertain a broad variety of partnerships including high-throughput screening of large collections of previously screened natural extracts, the Seeker is not interested in funding exploratory research. The Seeker as a business has commercial interest for solutions that could or do have incidental reports of control of several dicot and monocot weeds, such as Taraxacum spp., Trifolium spp., Bellis perennis, Plantago species, Cerastium species, Ranunculus spp., Glechoma spp, and other dicot weeds. Grass weeds to be controlled would include but not be limited to Digitaria spp. and Poa annua. The Seeker envisions, from a commercial standpoint, that the ideal solution should be selective in cool and /or warm season monocot turf grasses species and varieties such as Lolium perenne, Poa pratensis, Agrostis spp and Festuca spp and Cynodon dactylon and Zoysia spp. While the Seeker recognizes that this is a very difficult objective, it is important to set commercial goals and expectations now before a partnership is forged. Additional requirements of the project once completed are: The natural herbicide solution should include only active ingredient derived from natural origin such as secondary metabolites from microorganisms or plants extracts. If the solution is an active ingredient that cannot be produced on a commercial scale by extraction from plant materials or by fermentation it should be produced at least by chemical synthesis and be 100% identical to the naturally derived structure. The approach can be also based on a living microorganism, however the microorganism should not be genetically modified organisms (GMO). Mutants selected after using mutagenic agents such as UV light are also considered GMO. The proposed solution should have the possibility to be applied with conventional application equipments/ technologies such as sprayers or granule delivery systems or by drench. If not, the proposal should include application solutions. The solution should have an option for an identifiable, continuing and substantial natural supply (preferably from several sources) or an option to produce it. The proposed solution should be have a shelf life of a minimum of 2 years, ideally 3 years, as defined by less than 10% loss in activity or efficacy. The proposal should include with regard to the specific compounds or chemistries proof of principle, effectiveness data (especially any field data) and toxicity data. The solution should not be especially toxic to mammals. Requirements for a Partner: (not absolutely required but preferred) The partner should be skilled in one or more of the following areas or equivalent: natural product, agriculture. The partner should be able to work closely with the Seeker in pursuing the technology in question. Partners who are selected by the Seeker may be engaged for up to one year in a project. This is an electronic Request-for-Partners (eRFP) Challenge. The Solver shall write a preliminary proposal (about 2-4 pages including contact information) that focuses on a novel, previously unexplored approach or chemistry that will be evaluated by the Seeker with a goal of establishing a collaborative partnership. This proposal will also provide foundational information for longer-term IP relationships between the Seeker and the Solver(s). Upon completion of the evaluation, the Seeker may contact selected Solvers directly to work out terms for a collaboration contract. The monetary value of the contract and relationship will vary depending on the amount of work to be delivered and the time frame agreed upon. Project Criteria The Seeker, a Fortune 500 company, is looking for one or more collaboration partners to help identify and develop naturally occurring herbicides from any and all sources. It is well understood by this Seeker that there are relatively few natural herbicides for eradication of weeds or other invasive plants species and that those that are used today can be harmful if applied under the wrong conditions. This is an electronic Request-for-Partners (eRFP) Challenge; the Solver will only need to submit a written proposal to be evaluated by the Seeker with a goal of establishing a collaborative partnership. The submitted proposals should include two parts: Collaboration Proposalincluding: A brief discussion of a method that might be useful to the Seeker. The Solvers are not expected to provide a complete solution to the problem, but, rather, to present an approach that has potential to meet the requirements and could be pursued with the Seeker in collaboration. They should include the rationale of why their potential solution would work. The Solvers can withhold proprietary information, if necessary, but should provide enough information for the Seeker to appreciate the merits of their approach; A brief discussion of capabilities and prior experience as related to the problem including a publication list of relevant studies in this domain. The Solvers should explain what they can provide and what might be required from the Seeker. For example: “I can provide samples, but I would need the Seeker to design and run the efficacy testing”; A brief overview of the project (deliverables, timelines, milestones). General Information about the Solver including: Organization/Company/University name and address (including website, if available); The key contact person for this Challenge (including phone number and email address). (Note: For most Challenges, Solvers are not allowed to include personal contact information; however, for an eRFP Challenge, it is required.) How eRFP Challenges work: In contrast with other types of Challenges, there is no a predetermined Award for eRFP Challenge. The potential award would be a contract with the Seeker on mutually agreeable terms and conditions (to be negotiated) to conduct collaborative work and/or to provide materials and services to the Seeker in the future. After the deadline, all proposals will be forwarded to the Seeker for evaluation. If the Seeker identifies the Solver as a potential partner, they will contact the Solver directly to discuss the potential partnership and terms of any contract. Neither party is obligated to work together until a mutually agreeable contract is agreed upon.

一家全球性的公司正在寻找一项创新的下一代DNA测序技术来进行合作开发，公司可以和合作伙伴共同开发这项新的技术或者帮助伙伴申请许可。要求关于这个创新技术能有一个详细的说明，并且可以运用任何数据来支持这个新的技术。保证至少会奖励一名合格者。 征稿件请直接上传网址：https://www.innocentive.com” Partnering to Develop the NEXT DNA Sequencing Technology TAGS: Food/Agriculture, Nature, Chemistry, Life Sciences, Global Health, Ideation AWARD: $15,000 USD | DEADLINE: 12/19/12 | ACTIVE SOLVERS: 21 | POSTED: 11/19/12 The Seeker is a global company looking for truly novel ‘Next Generation Sequencing’ technologies that it can help to co-develop or in-license. A description of the technology is required, along with any existing data to support proof-of-concept. This is an Ideation Challenge with a guaranteed award for at least one submitted solution. Detailed Description & Requirements Background Next Generation Sequencing technologies have revolutionized the field of genomic studies – entire genomes can now be accurately sequenced in about a day and with only a few skilled manual steps. The speed and resolution of NGS technologies enables rapid tests to diagnose either infectious or inherited diseases as well as truly personalized medicine, where therapies are selected or optimized based on the patient’s DNA sequence. The Seeker wishes to identify concepts for novel NGS technologies and partners who can collaborate with the Seeker to develop those technologies. The Seeker is a truly global company with a multimillion US dollar annual R&D spend. The Problem A diverse array of NGS technology platforms are commercially available. The Seeker does not wish to use established, or commercially available, NGS technologies. Instead, they wish to partner with researchers, startup companies or universities to develop THE NEXT NGS technology. The technology you propose should be patentable or embody intellectual property owned by you or the institution you represent. The Solution The Seeker wishes to understand the concept of the proposed sequencing technology and to make an informed assessment of its merits. By responding to this challenge you entitle the Seeker freedom to practice the technology you describe in the proposal. The Seeker does not intend to copy your technology on its own, but intends to develop suitable technology in partnership with successful Solvers. Your proposal needs to give the Seeker enough information that it is confident to move forward with contacting successful Solvers and initiating confidentiality agreements so that negotiations may begin. The Seeker believes an ‘ideal’ proposal would describe: A sequencing technology that: Could sequence a full human genome in less than 1 day (>100 Billion bases per day) Has the potential to achieve an accuracy of at least 99.9 % Is amenable to full automation Can offer a consumables price significantly below $3,000 USD per 30x human genome (i.e., $30 USD per billion bases) The Seeker intends that promising emergent technologies or concepts will be co-developed with Solvers who have access to suitable resources. The Seeker has a considerable budget available to fund technology development once agreements are made with suitable Solvers. Submitted proposals should not include any information the Solvers may consider as their Intellectual Property that they do not want to share. Project Criteria Your proposed solution should contain: A description of the proposed novel sequencing technology and its mechanism Insights into any proof of concept data Reference to literature to support the viability of the proposed technology Insights regarding how the proposed technology differs from existing intellectual property & who owns any IP rights to the proposed technology A description of how you would develop the technology A rough idea of how many years it would take to reach proof-of-concept, prototype and full commercialization milestones along with an estimate of how much it would cost for any or all of these steps A summary of your expertise and resources as relevant to the technology Submitted proposals along with all relevant supporting data should include the information described in the Detailed Description of the Challenge. Submitted proposals should not include any personal identifying information the Solvers do not want to make public, or any information the Solvers may consider as their Intellectual Property that they do not want to share. This is an Ideation Challenge, which has the following unique features: There is a guaranteed award. The awards will be paid to the best submission(s) as solely determined by the Seeker. The total payout will be $15,000 with at least one award being no smaller than $5,000 and no award being smaller than $1,000. The Solvers are not required to transfer exclusive intellectual property rights to the Seeker. Rather, by submitting a proposal, the Solvers grant to the Seeker a royalty-free, perpetual, and non-exclusive license to use any information included in this proposal. After the Challenge deadline, the Seeker will complete the review process and make a decision with regards to the Winning Solution(s).All Solvers that submitted a proposal will be notified on the status of their submissions; however, no detailed evaluation of individual submissions will be provided.

什么样的顺序和结构性因素会影响小肽服用后的生物利用度? 哪些生理数据能确定肽被服用后是否进入到全身血液循环? 哪些模型能够用于评估肽的生物利用度? 这项任务是要求从相关的出版物，硅片模型和现有的研究数据中总结出有建设性的结论，提交一份书面建议书。 “征稿件请直接上传网址：https://www.innocentive.com” Understanding Bioavailability of Peptides TAGS: Nature, Global Health, Life Sciences, Food/Agriculture, Chemistry, Theoretical-licensing AWARD: $20,000 USD | DEADLINE: 1/09/13 | ACTIVE SOLVERS: 35 | POSTED: 11/09/12 What sequence and structural factors influence the bioavailability of small peptides following ingestion? Which physiological parameters determine whether peptides reach and persist in the systemic circulation, and which models would be relevant to assess peptide bioavailability? The Seeker is looking for insightful submissions that are supported by peer-reviewed publications, in-silico modelling &/or existing research data. This Challenge requires only a written proposal. Detailed Description & Requirements Background Hydrolysed milk proteins are used both in infant feeds and other food products. Either heat and pH or enzymatic processes are used to hydrolyze whey or casein proteins to smaller peptide species or single amino acids. These preparations contain peptides of 2-12 amino acids in length. While the mechanisms by which individual amino acids are absorbed and metabolized is well understood the knowledge about absorption mechanisms of peptides is much more limited. This Challenge requests in depth theoretical insights regarding which amino acid sequences or structures of casein-derived peptides and which physiological parameters are most influential in determining bioavailability. The focus is on bioavailability in human infants (0-2 years). Problem Bovine casein is a mix of AlphaS1, AlphaS2, Beta and Kappa-casein. Extensively hydrolysed casein contains a mixture of peptides 2-12 amino acids in length. Besides their established application in cow’s milk allergy, these casein hydrolysate derived peptides may have additional functionalities for human health in extra-intestinal tissues. These properties largely depend on their bioavailability and absorption characteristics as well as stability in plasma. Therefore, the main focus of this Challenge is whether these peptides can become systemically available intact – a prerequisite to exert bioactivity (in extra-intestinal tissues) related to specific health benefits. Well described physiological processes are known to result in digestion of proteins and peptides to individual amino acids, which are then taken up by the gut epithelium and from there into the blood stream. This digestive process and the uptake of amino acids is NOT the focus of the challenge. It is hypothesized that peptides from bovine casein hydrolysates can also become bioavailable from the gut, especially in infants in which the intestinal tract and the immune system are still developing. Which sequence motifs, or other characteristics of the casein-derived peptides influence their uptake from the gut lumen and subsequent systemic circulation? How could this be enhanced? Some critical parameters involved in this process may include, but are not limited to, peptide stability in the stomach and intestine, uptake by gut epithelia, transfer to the bloodstream and stability in plasma, resulting in distribution to other tissues. There is very limited evidence on transepithelial transport of casein-derived peptides and their systemic uptake into the blood, including e.g. measurements of plasma peptide concentrations after ingestion of a hydrolysate vs. the intact casein protein or detection of peptides in the apical/basal compartment. The Challenge The Seeker requires a comprehensive, evidence based understanding of the below questions: Which casein-derived peptides (2-12 amino acids long) can become systemically available intact after oral ingestion in infants (0-2 years)? Which properties of these peptides are crucial for their bioavailability and half-life in blood? Which physiological parameters during digestion, absorption and circulation determine whether peptides become systemically available? Which factors might increase peptide availability and stability in blood? What in-vitro or animal models and measurements are most useful in modeling systemic availability of small peptides in infant humans? It is likely that peptides of 2 – 12 amino acids may actively bind to and interfere with host cells. The Seeker is eager to predict the likelihood for uptake and gut-liver-blood passage, as well as systemic and central (brain) bioavailability of smaller peptides from an extensive casein hydrolysate. Exclusion criteria: The Seeker is NOT looking for information related to amino acid uptake and data related to the basic nutritional value of peptides as such. For possibilities to improve peptide availability and stability in blood, the Seeker is not interested in technologies such as encapsulation to improve gastrointestinal survival. Your proposal should fulfill the following Technical Requirements: The proposal should: Describe peptide structures, specific sequences or physicochemical parameters that are critical for systemic bioavailability of intact casein-derived peptides (2-12 amino acids in length) in human infants after oral intake.This proposal should be based on peer-reviewed literature, existing experimental data or in-silico assessments of bovine casein-derived peptides. Describe physiological parameters related to digestion, absorption and circulation that determine whether these intact peptides become systemically available and can be distributed to extra-intestinal tissues. Describe factors (such as supportive ingredients or technologies) that can support availability and systemic circulation of these intact peptides. Describe in silico, in-vitro or animal models and measurements that are relevant to better understanding bioavailabity of peptides ingested through the oral route. Animal or cell identity and genotypes/phenotypes should be disclosed as well as any proposed experimental protocols, end points and assay platforms / read out technologies. The seeker considers the following as ‘nice to have’: With regard to related health benefits, provide insights into bioactivity of casein hydrolysate derived peptides that can become systemically available. Project Criteria The submitted proposal should include the following: A comprehensive proposal that addresses each of the Technical Requirements listed above. Summary of the state of that art knowledge regarding the uptake and systemic distribution of casein hydrolysate derived peptides ingested through the oral route, including: Reference to peer-reviewed scientific literature or existing experimental data Reference to any in-vivo or in-vitro studies or in-silico predictive analyses. A description of your knowledge & expertise relevant to the challenge topic Your availability, in principle, to engaging with the Seeker in a contractual relationship The proposal should not include any personal identifying information (name, username, company, address, phone, email, personal website, resume, etc.) The Challenge award will be contingent upon theoretical evaluation of the proposal by the Seeker. To receive an award, the Solvers will not have to transfer their exclusive IP rights to the Seeker. Instead, they will grant to the Seeker non-exclusive license to practice their solutions.

PXE国际关于弹性假黄瘤(PXE)的研究团队，对其的病因提出了现有的两种假设：积极的循环代谢产物或者组织特异性功能障碍。任务要求提供数据来求证这两种假设或其中之一。根据各地的发病机制进行实验，进一步了解PXE的病因。 这项任务保证至少会奖励一名挑战者，并且，除了任务奖金之外，PXE国际还将对中标者给予PXE的研究经费资助。 征稿件请直接上传网址：https://www.innocentive.com PXE – Evaluating Hypotheses and Suggesting Experiments for a Rare Disease TAGS: Computer Science/Information Technology, Chemistry, Global Health, Nature, Public Good, Life Sciences, Ideation AWARD: $7,000 USD | DEADLINE: 11/30/12 | ACTIVE SOLVERS: 38 | POSTED: 10/31/12 The Seeker, PXE International, the primary group responsible for funding PXE research, presents two existing hypotheses (an active circulating metabolite(s) or a tissue-specific dysfunction) for the rare disease Pseudoxanthoma Elasticum (PXE). The Seeker requests that Solvers present evidence favoring one of the two hypotheses, then provide additional experiments to conduct to further knowledge around the disease mechanism. This is an Ideation Challenge with a guaranteed award for at least one submitted solution. In addition to the Challenge award, PXE International will also assist finalists in efforts to obtain funding for PXE-related research. Detailed Description & Requirements INTRODUCTION TO PXE Pseudoxanthoma Elasticum (PXE) is a recessive genetic disorder with signs and symptoms that mimic many aspects of the normal aging process, but at a much younger age (when people are roughly between 10 and 20 years old). Specifically, the disease is characterized by fragmentation and mineralization of elastic fibers in certain tissues. Some of the more common symptoms, in general order that they occur, are: Wet-type macular degeneration Skin wrinkling Calcification of blood vessels Cardiovascular disease PXE is a rare disease with an estimated patient population of 12,000 people. Given the small number of people with the disease, it has not been the subject of research by for-profit pharmaceutical and biotech companies. Research into PXE has generally been conducted by isolated labs without an overall guiding plan for finding the root cause of the disease and identifying proven treatments. CURRENT THEORIES OF DISEASE ORIGIN There are currently two general hypotheses regarding the cause of PXE – the metabolic theory and the tissue-specific theory. The metabolic theory is supported by the fact that 80% of people diagnosed with PXE exhibit a loss-of-function mutation in the ABCC6 gene which encodes the atypical, multi-drug associated, transmembrane transporter protein MRP6 (additional information available at http://www.ncbi.nlm.nih.gov/gene/368, and in the “References” document attached to this Challenge, some of which have links to free copies of the articles). This protein is normally expressed predominantly in the liver and kidney. The metabolic theory claims that the first step in the disease pathway is degradation and bioconjugation of a constituent of the extracellular matrix, specifically elastin. The theory further suggests that ABCC6 should remove this bio-conjugated metabolite but does not due to the mutation. Damage and remodeling of the extracellular matrix is then observed due to the elevated levels of this unidentified metabolite. The tissue-specific theory is also supported by the fact that 80% of people diagnosed with PXE exhibit a loss-of-function mutation in the ABCC6 gene, transmembrane transporter protein MRP6 in multiple organ and tissue systems, including the liver. In contrast to the metabolic theory, the tissue-specific theory claims that disease manifestations in the multiple organ systems (e.g., ocular, cardio, vascular, and gastrointestinal) and the tissue-dependent loss of expression are associated with extracellular matrix damage observed. The theory further suggests that the ABCC6 loss of function at the local affected tissues is essential to the disease pathogenesis beyond the metabolic insult resulting from the loss of function in the liver. KEY DATA A large amount of data from research on PXE, webinars, and links to further information may be found on the PXE International website at: http://www.pxe.org/research. Some key research and complications regarding the two general hypotheses are summarized below (multiple references concerning animal models of PXE are included in the “References” Word document attached to this Challenge, some of which have links to free copies of the articles): Preliminary experiments to identify the endogenous substrate of ABCC6 were carried out using insect reverse-transport vesicles. The results of a high-throughput screen, however, were that the protein was very promiscuous. A remaining question is how relevant these studies are to the human liver. An ABCC6 knock-out mouse has been created. Direct analysis of disease progression in this mouse, however, is complicated by up-regulation of sister proteins of ABCC6 and activation of additional pathways due to cell damage. One particularly interesting observation that has been made is that conjoining a wild-type and ABCC6 knock-out mouse results in both reversal of the PXE symptoms as well as no further disease progression in the knock-out mouse. Multiple transgenic mouse models have successfully mimicked the human PXE phenotype (mineralization of the elastin fiber in extracellular matrix). THE CHALLENGE PXE International, the Seeker for this Challenge, is requesting two items from Solvers: Well-reasoned proposals that support or refute one of the two general theories on the root cause of PXE that are consistent with the existing data or identify flaws in experiments that are inconsistent with the Solvers’ arguments. Suggestions of further experiments that could be conducted to aid in expanding knowledge about the cause of PXE, and that would ideally provide the basis for research into therapies for the disease. Submissions to this Challenge will be judged based on how convincing the Solver’s arguments are, how consistent the Solver’s arguments are with all known data, and how complete the submissions are. In addition to providing the two items listed above, Solvers are encouraged to also state whether they have the expertise, experience, and facilities to conduct the further experiments they propose. While this is not a factor that will be used to determine the award(s) for the Challenge, PXE International intends to assist finalists in securing funding to pursue their research if the Solver(s) are willing and able. ABOUT THE SEEKER PXE International was founded in 1995 to promote research and support individuals affected by pseudoxanthoma elasticum (PXE). They work on behalf of individuals and their families, to improve quality of life, through advancing research, educating clinicians and supporting individuals. We strive to provide the most up-to-date information about the disorder and the research being conducted around the world. Since many websites provide faulty or even erroneous information about diseases and treatments, it is important for PXE International to constantly update information regarding PXE as a resource for patients, medical professionals, and researchers. PXE International is the prime force in conducting basic and clinical research and providing financial support for applied translational research, product development, and treatment development for PXE. We steward the intellectual property to equitably advance products and services around the world for the individuals and families living with PXE. Project Criteria The Seeker, PXE International, presents two existing hypotheses (an active metabolite or a tissue-specific dysfunction) for the rare disease Pseudoxanthoma Elasticum (PXE). The Seeker requests that Solvers evaluate the two hypotheses, present evidence favoring one of the two, then provide additional experiments to conduct to further knowledge around the disease. Submitted proposals along with all relevant supporting data should include the information described in the Detailed Description of the Challenge. Submitted proposals should not include any personal identifying information the Solvers do not want to make public, or any information the Solvers may consider as their Intellectual Property they do not want to share. This is an Ideation Challenge, which has the following unique features: There is a guaranteed award. The awards will be paid to the best submission(s) as solely determined by the Seeker. The total payout will be $7,000, with at least one award being no smaller than $5,000 and no award being smaller than $1,000. The Solvers are not required to transfer exclusive intellectual property rights to the Seeker. Rather, by submitting a proposal, the Solvers grants to the Seeker a royalty-free, perpetual, and non-exclusive license to use any information included in this proposal. In addition to the Challenge award, the Seeker will also assist finalists in efforts to obtain funding for PXE-related research. After the Challenge deadline, the Seeker will complete the review process and make a decision with regards to the Winning Solution(s).All Solvers that submitted a proposal will be notified on the status of their submissions; however, no detailed evaluation of individual submissions will be provided.

摘要： 这项任务是寻找一种新的配方，合成除虫菊酯缓释制剂。 要求改变其生物活性化合物的挥发，使其的生物活性超过一年。这项配方必须要有足够的稳定性，即使是在热带环境中放几年也不受影响。并且所得的制剂在跟水稀释后能喷洒或涂刷在表面。要求这个配方必须使用常用的材料和国家最先进的制造工艺，并且对人体和环境是安全的。 这项任务需要提交一份详细的书面报告。 具体要求： Sustained Release Formulation for Synthetic Pyrethroids TAGS: Food/Agriculture, Chemistry, Physical Sciences, Theoretical-IP Transfer AWARD: $25,000 USD | DEADLINE: 12/16/12 | ACTIVE SOLVERS: 10 | POSTED: 10/16/12 The Seeker is looking for a novel formulation that modifies the volatility of a biologically active compound to give a product with activity of more than one year. The formulation should be stable for several years of storage even under tropical conditions. The resulting formulation should be able to be applied by spraying or by brushing etc. after dilution with water on many surfaces. The Seeker requires that the formulation technique must use commonly available materials and state of the art manufacturing process, as well as be safe for humans and the environment. This Challenge requires only a written proposal. Sustained Release Formulation for Synthetic Pyrethroids Detailed Description & Requirements INTRODUCTION The Seeker is keenly interested in finding a “new and novel” approach to formulation that will stabilize a volatile synthetic bioactive, for a full year after application via sprayed or brushed-on use scenarios, yet protected from its typical routes of decomposition. The formulation must be considered safe for humans and the environment, and it must be cost-effective to manufacture from commodity-type materials using state-of-the-art manufacturing processes. DETAILS OF COMPOUND TO BE FORMULATED The active the seeker is interested in belongs to the chemical class of synthetic pyrethroids (http://en.wikipedia.org/wiki/Pyrethrin). It has a molecular weight of approx. 400, a vapor pressure of about 1mPa at 25°C, a very poor solubility in water but high in non-polar media. Types of Pyrethroids the Solver can search for background information Allethrin Bifenthrin Cyfluthrin Cypermethrin Cyphenothrin Deltamethrin Esfenvalerate Etofenprox Fenpropathrin Fenvalerate Flucythrinate Imiprothrin lambda-Cyhalothrin Metofluthrin Permethrin, dichlorovinyl derivative of pyrethrin Prallethrin Resmethrin Silafluofen Sumithrin tau-Fluvalinate Tefluthrin Tetramethrin Tralomethrin Transfluthrin ADDITIONAL CONSIDERATIONS The product should be applied by spraying or brushing from aqueous solutions or dispersions on different surface types and should be available for uptake by insects and other arthropods during the entire period of performance. The Solvers should understand that the Seeker is in the business of chemical formulation and is not seeking a detailed literature review of the existing technologies for formulation of pyrethroid chemistries. What the Seeker is looking for is an application of an orthogonal approach or a method that is not standard or used in the industry. Out-of-the-box thinking and applications are sought with both human safety and the environment health kept in mind. Technical Requirements for Theoretical Solution No original data or experiments need to be performed in order to qualify for the award but the solution should address the following Technical Requirements. Stability Prior to Application - The proposed new or novel formulation must be chemically and physically stable for several years on the shelf before application. Percentage of Active - The proposed new or novel formulation must contain between 5 and 1 % of the active ingredient. Water-Mixing Considerations Particle Size - Upon diluting the original formulation to 1% in water, all particle sizes should be less than 20 micrometers. Final formulation particle size must not be in the nanometer size range from a health safety standpoint. No Oil-in-Water Emulsions – The final product for application should not be an oil-in-water emulsion spray solution in order to avoid the secondary impact of oil on contacted surfaces. Application Methods - The proposed new or novel formulation must be sprayable or brushable after dilution with water. An example of the equipment for application for the final diluted formulation might be using a common knap-sack sprayer type equipment. Surfaces to be treated - Once sprayed, the active must remain available to the insect at an effective concentration on all different surfaces with different porosities and surface chemistries (e.g., wood, mud, concrete, PVC). Novelty – The Seeker is well aware of known methods in the formulation as well as polymer-embedding literature (patents [issued and even pending] and scientific literature). Legal – The proposed solution should offer the Seeker freedom to practice. That is, solver proposed solution should not be encumbered by existing patents that would block the Seeker from using the formulation. Ideally, a solution would offer the Seeker the rights to patent the idea themselves if they can demonstrate its effectiveness. The Solvers should understand that the Seeker is in the business of chemical formulation and is not seeking a detailed literature review of the existing technologies for formulation of pyrethroid chemistries. What the Seeker is looking for is an application of an orthogonal approach or a method that is not standard or used in the industry. Out-of-the-box thinking and applications are sought with both human safety and the environment health kept in mind. If multiple proposals meet all the Technical Requirements, the Seeker reserves the right to award only the solution, which they believe, is most likely to be successfully and cost-effectively implemented. Project Criteria This requires only a written proposal. The proposal should include the following: Identification/Detailed Description of a technology/method that can meet the Technical Requirements as explained above. Rationale as to why the Solver believes that the proposed solution will work including citations and references to publicly available literature. This rationale should address each of the Technical Requirements described in the Detailed Description and should be supported with relevant examples and literature citations and data. NOTE: The Seeker considers the explanation to be the most important part of this Challenge. Please be sure your explanation is clear and your argument is strong (backed by references, data) to convince the Seeker it will work. The proposal should not include any personal identifying information (name, username, company, address, phone, email, personal website, resume, etc.) All proposals will be rated solely on the strengths of the theoretical proposal. While it is important for the Solver to demonstrate a technically solid approach via references to published studies, no independent experimentation is required from the Solver. The Challenge award will be contingent upon theoretical evaluation of the proposal by the Seeker. If multiple proposals meet all the Technical Requirements, the Seeker reserves the right to award only the solution, which they believe, is most likely to be successfully and cost-effectively implemented. To receive an award, the Solvers will have to transfer to the Seeker their exclusive Intellectual Property (IP) rights to the solution.

最近在美国，天然气的可用性范围大大提高。这将潜在的影响天然气转化成化学物质的进程，比如目前来自原油的烯烃和芳烃。这个任务就是需要找到使天然气转换成主要的化学和化工原料的新方法。 这是一个思维方法的挑战，保证至少会奖励一名合格者。 应征稿件请直接上传网址：https://www.innocentive.com Natural Gas Conversion to Chemicals TAGS: Engineering/Design, Chemistry, Physical Sciences, Ideation AWARD: $15,000 USD | DEADLINE: 10/28/12 | ACTIVE SOLVERS: 126 | POSTED: 9/28/12 Recent developments show a large increase in Natural Gas (NG) availability in the US. This leads to the potential for processes to convert NG to chemicals that are currently derived from crude oil such as olefins and aromatics. The Seeker is looking for novel ideas for methods to convert Natural Gas to a major chemical or chemical feedstock beyond those processes known today. This is an Ideation Challenge with a guaranteed award for at least one submitted solution. Detailed Description & Requirements Background Recent developments show a large increase in Natural Gas (NG) availability in the US; novel production methods to extract NG from shale reservoirs have reversed forecasts from the US becoming a net gas importing to a net gas exporting country. On the demand side, gas utilization is favored because it has the lowest CO2 emissions /energy ratio. At the same time, crude oil availability (as simply observed from its price) has been limited. In general, the gas-oil differential has been widening in the recent past and there are reasons to believe this broad gap will be continued well into the future. This outlook offers interesting potential for processes to convert NG to products that are currently derived from crude oil, e.g. (liquid) transportation fuels and chemical feedstock as olefins and aromatics. Some processes already exist, for example: Gas-To-Liquids, GTL, process converting NG via synthesis gas intermediate (a mixture with varying ratios of hydrogen and carbon monoxide, often containing carbon dioxide as well) to paraffinic products using Fischer-Tropsch synthesis. These are further reacted to naphtha, diesel and base oils. Methane to synthesis gas intermediate can be reacted to (liquid) methanol that is a starting material for making a wide variety of commodity chemicals. Methane pyrolysis to acetylene with subsequent hydrogenation to ethylene. Methane to synthesis gas intermediate directly to various chemicals. The direct conversion of methane, the major constituent of NG, with oxygen to methanol or higher hydrocarbons as ethane and especially ethylene (and water) is the “holy grail” in transforming NG to crude oil types of products. Although the term ‘ synthesis gas’ very well describes the versatility of this mixture to build a number of valuable chemicals, its use always requires multi stage process as NG gasification or Steam-Methane-Reforming (SMR) to make the synthesis gas, followed by one or more dedicated conversion processes. Despite considerable effort, a direct route of methane to petrochemicals has not been developed into a commercially viable process. The main reason is that the yield of products, being methanol or ethane, ethylene and higher hydrocarbons is less than 25% based on the methane being converted per pass. This Challenge addresses the need for ideas that would result in the design of a direct methane conversion process that breaks this 25% yield barrier. The Seeker is canvassing for novel concepts, as many ideas in this technical area of methane conversion have been worked on and are well known. We encourage participation on this Challenge from both those inside and outside the traditional methane-conversion field. The Challenge The Challenge is to come up with a method that would result in the conversion of methane into a major chemical (e.g. ethylene, benzene) or into a standard feedstock used to make these major chemicals (e.g. ethane, propane) or some combination of the two. Any method should have the ability to reach a single pass yield of > 20% and preferably >25%. Although the Seeker is primarily concerned with direct methane conversion pathways, suggestions around improved methods in making synthesis gas will be considered if they are more efficient than conventional technologies. Things to avoid: The Seeker is not interested in stoichiometric reagents using halogens or sulfur, however methods utilizing catalytic amounts of these reagents will be considered. The Seeker is less interested in known technologies in the open literature; however if the method significantly improves a known process that may be acceptable. (For example: yield improvements above and beyond reported in literature) Any proposal should address as many of the following Technical Guidelines as possible. The method must result in the conversion of methane to one of the following: One of 8 major chemicals; ethylene, propylene, benzene, toluene, xylenes, butadiene, styrene, or methanol. Standard feedstock used to make these 8 chemicals such as ethane, propane, aliphatics or mixtures thereof. Any combination of a. and b. Any direct methane conversion method must result in a single pass yield of >20% (preferably >25%). Single pass yield targets will be very dependent on product composition, selectivity and ease of separation so preference will be given to technologies that improve those issues. A strong preference will be given to a method that does not rely on a significant fraction of non-commercially developed technologies to enable the fully envisioned commercial process. For example, it would be acceptable if the novelty part of a solution is described in the reactor, but conventional separations can be utilized… or vice versa. It would be significantly more challenging if both the reactor and separations require development for commercialization. Put another way, if the method includes three steps in a process with only one step as novel (to be developed) and two steps use standard, known technologies, then this method would be favored over a three step process where all three steps were novel. Solutionsusing oxygen as an activation agent are preferred. Solutions with other activation agents are allowed with the exceptions of stoichiometric activation by halides or sulfur-containing compounds (as described above). It would be preferred, but not absolutely necessary, that a method already has some proof of concept work completed, such as experimental data showing methane conversion and selectivity to reaction products. It is preferred that the Solver can articulate a complete process. However, ideas focusing on any one or combination of methane activation, methane conversion, reactor design, or separations are welcome. Project Criteria The proposal should include the following information: Detailed description of the proposed novel method/process that can convert NG into chemicals as described above. Rationale as to why the method/process can meet the Technical Guidelinesabove. Your response should cover each Requirement. Please provide any proof of concept data that might exist. If no data exists, please list the experiments/work needed to demonstrate the proof of concept. Submitted proposals should not include any personal identifying information the Solvers do not want to make public, or any information the Solvers may consider as their Intellectual Property they do not want to share. This is an Ideation Challenge, which has the following unique features: There is a guaranteed award. The awards will be paid to the best submission(s) as solely determined by the Seeker. The total payout will be $15,000, with no award being smaller than $5,000. The Solvers are not required to transfer exclusive intellectual property rights to the Seeker. Rather, by submitting a proposal, the Solvers grants to the Seeker a royalty-free, perpetual, and non-exclusive license to use any information included in this proposal. After the Challenge deadline, the Seeker will complete the review process and make a decision with regards to the Winning Solution(s). All Solvers that submitted a proposal will be notified on the status of their submissions; however, no detailed evaluation of individual submissions will be provided.

实验室拟邀请4位研究人员进行他们的研究项目。研究地点是在位于西班牙的葛兰素史克公司的药物开发园。研究人员的生活费，旅游资金，住宿费和研究所花的耗材成本皆由实验室承担。4个研究项目，每一个都有16万美元的预算。任务要求：需要有疟疾病，肺结核病和动质体疾病(南美锥虫病，利什曼病，昏睡病)等领域的开放性的研究。这项挑战的优胜者请直接联系实验室，以便根据他们的反馈和指导，做出更全面的考虑。这是一项寻找合作伙伴的任务，要求提交一份书面企划书以做评估。 Tres Cantos Open Lab Foundation: Proposals for Neglected Diseases Research TAGS: Developing Countries, Requests for Partners and Suppliers, Life Sciences, Food/Agriculture, Nature, Global Health, Computer Science/Information Technology, Chemistry, Physical Sciences, Public Good, eRFP AWARD: varies | DEADLINE: 10/29/12 | ACTIVE SOLVERS: 92 | POSTED: 9/17/12 The Tres Cantos Open Lab Foundation intends to invite up to 4 Solvers to conduct their research projects using the facilities and resources of GlaxoSmithKline’s Tres Cantos Medicines Development Campus in Spain. Researcher subsistence, travel, accommodation & consumable costs can be covered by the Tres Cantos Open Lab Foundation. Four research projects are budgeted for, each having a maximum funding of $160,000. Proposals for groundbreaking research in the areas of malarial disease, tuberculosis and kinetoplastid diseases (Chagas Disease, Leishmaniasis or Sleeping Sickness) are required. The winners of this challenge will be contacted directly by the Tres Cantos Open Lab Foundation in order to make more comprehensive proposals based on their feedback and guidance. This is an electronic Request-for-Partners (eRFP) Challenge; the Solver will only need to submit a written proposal to be evaluated by the Seeker with a goal of establishing a collaborative partnership. Source: InnoCentive Challenge ID: 9933167 Challenge Overview Are you a researcher who would like to spend from 6 to 24 months at the world class facilities of the open lab at GSK’s Tres Cantos Medicines Development Campus in Spain carrying out research that will positively impact the lives of people in the developing world? Funding for up to 4 research projects totaling up to $160,000 each are available for the best research proposals relevant to malarial disease, tuberculosis or kinetoplastid diseases (Chagas disease, Leishmaniasis or Sleeping Sickness). Research projects can last from between 6 to 24 months and researcher subsistence, travel, accommodation and consumables costs can be covered by the Tres Cantos Open Lab Foundation. This is an electronic Request-for-Partners (eRFP) Challenge. The Solver will write a preliminary proposal (about 2–4 pages including contact information) to be evaluated by the Seeker with a goal of establishing a collaborative partnership. Upon completion of the evaluation, the Seeker may contact selected Solvers directly to work out terms for a collaboration contract. The monetary value of the contract will vary depending on the amount of work to be delivered and the time frame agreed upon. Funding for up to 4 research projects totaling up to $160,000 each is available for the best research proposals TheSolvers are not required to transfer exclusive intellectual property rights to the Seeker. However, it is a requirement of funding that any intellectual property developed as result of any funding be made broadly available to further research in Neglected Tropical Diseases, and therefore the Solvers will be required to make their results available through WIPO Re:Search (http://www.wipo.int/research/en/about/guiding_principles.html). The Seeker is currently supporting other projects in this field and desires to maintain its ability to support other proposals for funding, therefore Solvers are requested not to include any confidential information in their initial proposals. (NOTE: only proposals from Solvers who have the ability to work as the collaboration partner will be considered.) Detailed Description & Requirements The Tres Cantos Open Lab Foundation aims to accelerate the discovery and development of medicines to tackle diseases of the developing world in an open and collaborative way. Through the connection to the GlaxoSmithKline’s (GSK) specialist Tres Cantos Medicines Development Campus in Spain, scientists funded by the Foundation can gain access to the available resources and facilities and work alongside the scientists at the campus. Researchers are able to access GSK’s expertise, processes, and industrial-scale infrastructure as part of a collaborative approach to drug discovery. Subsistence, travel, accommodation and consumable budget expenses can be covered by the Tres Cantos Open Lab Foundation. The Tres Cantos Open Lab Foundation was set up by GSK in 2010 and is registered as a charity in England and Wales No. 1142577. Solver Eligibility To be eligible for funding by the Tres Cantos Open lab Foundation, Solvers must: Be affiliated with an academic, a public or an industrial research institute Have a proven track record relevant to the proposed research in any one or more of the following fields: Malaria Tuberculosis Kinetoplastids (Chagas Disease, Leishmaniasis or Sleeping Sickness). Be available to conduct their research at the Tres Cantos Campus, Spain for the time needed to execute the proposal Scope of Research Proposals Requested The Tres Cantos Open Lab Foundation wishes to receive innovative proposals that will advance discovery or development of therapies for Malaria, Tuberculosis and Kinetoplastid diseases. The following aspects of drug discovery for these therapeutic areas are of particular interest, but proposals addressing other aspects are very welcome: Dissection of pathogen or host immunological pathways in order to identify potential therapeutic targets. Physiologically relevant models of disease that may be amenable to screening or prioritization of chemical entities. New chemical entities that target pathogen replication, transmission or human pathology. Your proposal should fulfill the following Technical Requirements: Be relevant to accelerating the discovery or development of therapeutic approaches for Malaria, Tuberculosis of Kinetoplastids. Be feasible to be conducted in the Tres Cantos Medicines Development Campus from the technological point of view. Be innovative in tackling one unmet goal in the concerned disease (e.g. malaria transmission blocking, radical cure of malaria infections caused by P. vivax, short treatment for MDR (multi drug resistant) - TB, a good and predictive physiological model of the disease for screen, new and better drugs to treat any of the kinetoplastid diseases, etc) Project Criteria Funding for up to 4 research projects totaling up to $160,000 each are available for the best research proposals relevant to tuberculosis, malarial disease or kinetoplastids. Your Research Proposal must be submitted no later than October 30th & should contain: A 1-2 page summary of the proposed research, including: A 1-paragraph executive summary Background information describing the working hypothesis behind the proposal citing 3-10 peer-reviewed publications that support the proposal A bullet list outlining core phases of the proposed research Brief descriptions of techniques and technologies key to implementing the research plan A 1-page description of your experience and expertise relevant to carrying out the proposed research, including publications, if applicable. A statement of your availability to execute the proposed research at the Tres Cantos Medicines Development Campus, including the available timeframe and any special requirements you may have. Appendices may be added if directly relevant e.g. for inclusion of existing but unpublished experimental data that supports your proposal. How eRFP Challenges work: In contrast with other types of Challenges, there is no a predetermined Award for eRFP Challenge. After the deadline, all proposals will be forwarded to the Seeker for evaluation. If the Seeker identifies the Solver as a potential partner, they will contact the Solver directly to discuss the potential partnership and terms of any contract. Neither party is obligated to work together until a mutually agreeable contract is agreed upon.

“科技每年都会见证一些神奇的真理和制造出令人眼花缭乱的东西,如吴雨霏穆利斯《创新的聚合酶链式反应》。 不幸的是，他们中的大多数被淘汰出局。而聚合酶链式反应则预示着基因组的革命. 这是一项关于思维的挑战，这项任务要求挑战者来概述制药行业需要采取哪些创新，来适应这优胜劣汰的游戏规则。挑战者不需要发表明确的解决方案，你只需要清楚的描述已经存在的，可能会成为下一个制药趋势的大事。这将有助于制药行业寻找明天的药物，生产新药。 What Disruptive Innovations Does Pharma Need To Discover Tomorrow’s Drugs? AWARD: $5,000 USD | DEADLINE: 10/15/12 | ACTIVE SOLVERS: 220 | POSTED: 9/14/12 Source: InnoCentive Challenge ID: 9932826 Type: Ideation Detailed Description & Requirements Background Productivity in drug discovery & development – the number of new drugs reaching patients – has been declining. At the same time, R&D spending has been increasing. Industry experts calculate the mean R&D spend per new drug on the market is $4-11 billion dollars. 2012 Forbes Article: The Truly Staggering Cost of Inventing New Drugs The Problem Various factors contribute to this high development cost. The most prominent is the high rate of attrition (failure) on drug like compounds as they pass through the drug development process. For every 10,000 compounds that appear interesting during basic research, 1 may reach market as an approved drug. Causes of compounds not progressing include: Lack of efficacy or potency Unfavorable pharmacology/pharmacodynamics Toxicity or safety Increasing regulatory stringency in approving drugs for clinical trial and for market Increasing emphasis on stratification of patient populations for administration of drugs (personalized medicine) Factors contributing to these causes include, but are not limited to: Assay systems and platforms that poorly replicate drug effects in humans Lack of new therapeutic drug targets being identified e.g. phenotypic screening data is difficult to convert into new molecular targets Animal experimental data, too, poorly predicts effects in humans / translational medicine Lack of good validated biomarkers to measure disease states or predict responses to drugs The Solution The Seeker requires your well thought out ideas and game changing approaches to help pharma address one of the following questions. Choose one of the following for your submission, describe your game changing solution & justify how it will address any one or more of the problem causes and factors listed above. Choose one of the following: What are the new game changers affecting how we find new drugs e.g. new in-silico modeling approaches, new biological sources or screens? What will be the next big technology that enables better drug candidates, molecular targets or biomarkers to be identified i.e. game changing technologies in molecular biology, synthetic chemistry, cell-based models? How could clinical trials be better designed and implemented i.e. faster, more cost effective or producing better data? How could best value be delivered top patients The Seeker is not interested in published approaches, suggestions of individual drug candidates, or specific assays – proposals describing novel, creative & GAME CHANGING innovations are required. You don’t need to invent the solution; you just need to clearly describe what is already out there that has the potential to become ‘the next big thing’ that will help make the Pharma industry more productive finding the drugs of tomorrow. Project Criteria Submitted proposals along with all relevant supporting data should include the information described in the Detailed Description of the Challenge. Your proposal should include: A detailed description of features of ‘the next big thing’, including Insights into how it addresses one or more of the causes and factors of the problem as outlined above An outline of what ‘the next big thing’ would enable for the pharma industry Any supporting evidence, such as reference to the literature (patent, commercial or academic). Submitted proposals should not include any personal identifying information the Solvers do not want to make public, or any information the Solvers may consider as their Intellectual Property they do not want to share. This is an Ideation Challenge, which has the following unique features: There is a guaranteed award. The awards will be paid to the best submission(s) as solely determined by the Seeker. The total payout will be $5,000, with at least one award being no smaller than $3,000 and no award being smaller than $1,000. The Solvers are not required to transfer exclusive intellectual property rights to the Seeker. Rather, by submitting a proposal, the Solvers grants to the Seeker a royalty-free, perpetual, and non-exclusive license to use any information included in this proposal. After the Challenge deadline, the Seeker will complete the review process and make a decision with regards to the Winning Solution(s).All Solvers that submitted a proposal will be notified on the status of their submissions; however, no detailed evaluation of individual submissions will be provided.

这项任务要要求设计一个自动化的，高通量的仪器 ， 可以定量地和可重复地测定的油水乳化液的分离。 这个任务需要提交一份书面建议书。 An Instrument for Quantitative, Reproducible Characterization of Water/Oil Emulsions AWARD: $30,000 USD | DEADLINE: 10/15/12 | ACTIVE SOLVERS: 508 | POSTED: 8/15/12 Source: InnoCentive Challenge ID: 9933086 Type: Theoretical-IP Transfer Detailed Description & Requirements The presence of emulsions in oil operations is common and generally undesirable. Crude oil emulsions typically form due to the presence of naturally occurring emulsifying agents (asphaltenes, resins, etc.) in crude oil. The high cost associated with transportation and corrosion of equipment is one of the problems caused by the presence of water in the crude oil. Therefore, oil dehydration is required, which is often achieved through chemical treatment using demulsifiers. While the Seeker has identified ~200 liquid “demulsifier” agents, compounds that in amounts of ~100-500 ppm can aid in the resolution of the water and oil phases, they lack a quantitative and reproducible assay for determining demulsifier effectiveness at resolving the emulsion. Currently, the Seeker performs a “bottle test” in which they add ~15-100 mL of the emulsion into a bottle, add the different demulsifiers, shake, and then visually observe which bottles show the best phase separation. This assay clearly relies on visual detection by a trained observer and is not nearly as quantitative or reproducible as the Seeker desires. Results from a bottle test with the same emulsion and three different demulsifiers are shown below. The bottle on the left has clearly not been resolved into two distinct phases. While the middle bottle shows significant improvement, careful inspection of the phase boundary shows a slight amount of oil contaminating the water layer and a slightly undefined interface. Finally, the bottle on the right shows an optimally resolved two-phase system with a very clear oil/water phase boundary. Important Note: While this mostly water emulsion has been used as an example, the Seeker’s emulsions can vary widely in terms of the oil and water percentages from roughly 10-90% oil and the remainder water. Finally, there are standards of purity for both the oil and water layers resulting from effective demulsification (see Solution Requirement #2 for details). The present state of the art is that the Seeker must remove an aliquot of each layer, then a person must perform additional testing to determine whether the purity requirements have been met. The Seeker desires an instrument that can perform this measurement directly on the emulsion sample. Accordingly, the Seeker desires designs for an automated high-throughput instrument that can quantitatively and reproducibly assay the separation of water and crude oil emulsions in the presence of a demulsifier. Solvers’ proposed instrument should meet the Solution Requirements listed below. Quantification of Emulsion vs Separated Layers– The instrument should quantify the degree of separation of the phases over time by measuring any property that can be related to the volume of the oil, water, and emulsion phases. Quantification of Layer Purity– The instrument should be able to quantify oil dryness and water cleanliness to at least a limit of detection required by existing benchmarks: Oil Layer – non-dissolved solids and water < 0.5% Water Layer - Total oil and grease < 29 ppm Precision– The instrument should provide reproducible results on the same emulsion, affording a precision of + 5% for both Requirements #1 and #2. Demulsifier Addition– The instrument should have a mechanism to allow for the accurate addition of liquid chemical demulsifiers (~10-100 microliters) to different emulsion samples without cross-contamination. Operating Conditions– The instrument must operate safely under the following conditions: Temperatures ranging from 25 ?C to 120 ?C Pressures ranging from 1 to 3 atmospheres Emulsion sample volume ranging between 15 and 100 mL Demulsifier addition cannot decrease sample pressure Ideally, the instrument would also be capable of agitating the samples for 1-15 minutes at variable speeds in order to aid in the dissolution of the demulsifier or create an emulsion starting from separated water and oil phases. Throughput– The instrument should be capable of testing at least 25 or more samples within 8 hours. Ideally, the instrument would require little or no operator intervention throughout this time. Cost– The instrument should not cost more than $125,000 to build. Intellectual Property– The Seeker should have the freedom to operate the instrument without being barred by any third-party patents. Ideally, the instrument would be able to be patented. Portability– The instrument would ideally be able to be readily packaged, transported, and configured for use in a new location with as little effort as possible. If multiple proposals meet all the Solution Requirements, the Seeker reserves the right to award only the solution which they believe is most likely to be successfully and cost-effectively implemented. Project Criteria The Seeker desires designs for an automated, high-throughput instrument that can quantitatively and reproducibly assay the separation of water and crude oil emulsions in the presence of a demulsifier. This is a Theoretical Challenge that requires only a written proposal to be submitted. The submitted proposal should include the following: A detailed instrument design that meets the Solution Requirements in the Detailed Description. Rationale as to why the Solver believes that the proposed instrument will work. This rationale should address each of the Solution Requirements described in the Detailed Description and should be supported with relevant examples, test protocols (i.e., how to carry out the actual experiment, how to calibrate equipment if needed, how to process the data, etc.), diagrams, and literature citations. If the complete system or part of it can be purchased from a third party, information about suppliers should be provided. The proposal should not include any personal identifying information (name, username, company, address, phone, email, personal website, resume, etc.) The Challenge award will be contingent upon theoretical evaluation of the proposal by the Seeker. If multiple proposals meet all the Solution Requirements, the Seeker reserves the right to award only the solution which they believe is most likely to be successfully and cost-effectively implemented. To receive an award, the Solvers will have to transfer to the Seeker their exclusive Intellectual Property (IP) rights to the solution. However, the Seeker will be willing to consider a licensingagreement for a partial award if exclusive IP cannot be transferred by the Solver.