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ISEB-SWTINT1 exam Dumps Source : ISEB Intermediate Certificate in(R) Software Testing

Test Code : ISEB-SWTINT1
Test cognomen : ISEB Intermediate Certificate in(R) Software Testing
Vendor cognomen : ISEB
: 43 existent Questions

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ISEB ISEB Intermediate Certificate in(R) launches original practising materiel | existent Questions and Pass4sure dumps

The ISEB check management certification is the subsequent even of competency in software checking out after the ISEB groundwork and ISEB Intermediate ranges. earning this certification makes employment candidates extra efficacious and marketable, because it signifies a strong potential to analyse, synthesize and deem projects concerning utility testing management. These competencies are vital to the career development of utility testers, primarily in this age of global competitors and economic uncertainty.

like several practicing applications, an accepted and totally skilled ISEB course tutor authored the ‘test administration’ path. The course is completely in line with the respectable ISEB exam syllabus and includes exciting researching materiel confirmed to maximise the absorption of the fabric.  This and complete different timehonored exams practising kits embrace an ironclad, a hundred per cent guarantee: move, or rep a complete refund, no questions requested.

“ became formed in 2001 with the purpose of creating QA certification cost-efficient,” observed advertising supervisor David L Brister. “up to now, the handiest actual strategy to prepare for a utility tester certification exam changed into to attend a dear two or three day instructor-led course. Their programs are assured to deliver the identical degree of coaching, at a fraction of the cost.”

The check management peruse at materiel contains a finished study guide, observe assessments, fifty six twin-sided flashcards, situation of affairs query papers, exam counsel, bounty material, 90 days complete training aid within the deepest zone of the enterprise’s IT certification forum, and extra. moreover, the materiel is available in distinctive dawn methods – immediate down load, set of CDs, or every exiguous thing supplied in a bound, complete colour booklet (with the bounty cloth on a CD).

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ISEB Practitioner commerce and solution structure | existent Questions and Pass4sure dumps

This supplier-selected Certification is offered by:British computing device Society (BCS)Swindon, Se UKPhone: forty four (0)1793 417417

skill degree: advanced                          fame: active

low-cost: not accessible               

abstract:For commercial enterprise and reply Architects who observe their intermediate even expertise to a case study and can tricky on the commerce enterprise and procedures required to control an architecture correctly. This certification is apropos for those who are engaged in any factor of commerce and solution structure.

initial requirements:You beget to pass the ISEB Practitioner in commercial enterprise and solution structure exam. The examination has a one hour time restrict and incorporates 40 diverse-option questions according to a case peruse at. A passing score of 26/40 is required.Six years of IS/IT travail event, together with some structure definition is suggested. it is additionally counseled you cling the ISEB Intermediate degree certificate, or beget studied the ISEB Intermediate stage Syllabus and Reference model, and beget both TOGAF eight or TOGAF 9 degree 2 certificate. working towards is purchasable but now not required.

carrying on with necessities:None exact

See complete British laptop Society Certifications

dealer's web page for this certification

what's ITIL? Your e engage to the IT Infrastructure Library | existent Questions and Pass4sure dumps

what's ITIL?

The IT Infrastructure Library (ITIL) is a library of volumes describing a framework of optimal practices for providing IT features. ITIL has gone through a number of revisions in its history and currently comprises five books, each and every covering various techniques and stages of the IT carrier lifecycle. ITIL’s systematic method to IT provider management can back organizations manage possibility, fortify customer relations, set up competitively priced practices, and construct a accountable IT ambiance that makes it feasible for for increase, scale and alter.

Developed through the British govt's crucial computing device and Telecommunications company (CCTA) complete through the Eighties, the ITIL first consisted of greater than 30 books, developed and launched over time, that codified most useful practices in counsel technology accumulated from many sources (including companies' premier practices) around the globe. IBM, as an instance, says that its 4-extent series on programs-management ideas, A administration materiel for suggestions systems, commonly used as the Yellow Books, offered a must beget enter into the long-established ITIL books.

In April 2001, CCTA, along with several different groups, were rolled into the workplace of government Commerce (OGC), which is now frequent as the cabinet office. The OGC adopted the mission as section of its mission to travail with the U.okay. public sector as a catalyst to achieve effectivity, value for funds in commercial activities, and more advantageous success within the dawn of classes and initiatives.

The goal wasn't to create a proprietary product that could be commercialized; somewhat, it changed into to collect pattern practices that could assist with what the executive recognized changed into an increasing dependence within the government on IT mixed with a painful necessity of universal techniques that had been increasing fees and permitting mistakes to perpetuate. It rapidly became manifest that distributing these top of the line practices would earnings each public and private-sector corporations.

over the years, ITIL's credibility and utility grew to become identified, and in 2005 its practices contributed to and aligned with the ISO/IEC 20000 carrier management average, the primary international universal for IT provider administration; it's in response to British universal BS15000.

considering the fact that 2013, ITIL is owned by means of Axelos — a joint venture between the cabinet workplace and Capita. Axelos offers businesses the license to manufacture expend of the ITIL framework, whereas managing updates and system adjustments. youngsters, to manufacture expend of ITIL internally, companies attain not beget a license. ITIL v3 became released in 2011, beneath the cupboard office, bringing updates to the 2007 edition posted below OGC.

In 2018, Axelos announced ITIL four – a expansive overhaul to the entire framework and the greatest alternate on the grounds that ITIL v3 became posted in 2007. ITIL 4, which began rolling out in Q1 of 2019, offers a greater agile, springy and customizable version of ITIL that is up to date for up to date agencies. The newest edition encourages less siloes, greater collaboration, communique throughout the all enterprise and integrating agile and DevOps into ITSM ideas.

What's within the ITIL?

The ITIL has passed through a number of revisions in its background. The fashioned 30 books of the ITIL beget been first condensed in 2000 (when ITIL V2 became launched) to seven books, each and every wrapped around a facet of IT management. Later, the ITIL Refresh mission in 2007 consolidated the ITIL to 5 volumes which includes 26 system and functions – this is observed as the ITIL 2007 version. In 2011, one more update — dubbed ITIL 2011 — became posted beneath the cupboard office. The 5 volumes remained, and ITIL 2007 and ITIL 2011 remained identical.

ITIL four, which turned into released in 2019, maintains the identical hub of attention on automating processes, enhancing carrier administration and integrating the IT offshoot into the company. despite the fact, it moreover updates the framework to accommodate and reply to modern expertise, materiel and application. considering ITIL’s ultimate replace, the IT offshoot has grown to eddy into vital to every company and the brand original framework incorporates this through being more agile, bendy and collaborative.

ITIL four incorporates nine guiding principles that had been adopted from probably the most recent ITIL Practitioner examination, which covers organizational trade management, communique and dimension and metrics. These ideas include:

  • center of attention on cost
  • Design for event
  • delivery where you are
  • Work holistically
  • growth iteratively
  • look at directly
  • Be transparent
  • Collaborate
  • retain it standard
  • The most up-to-date version of ITIL makes a speciality of enterprise tradition and integrating IT into the timehonored company structure. It encourages collaboration between IT and other departments, principally as other company gadgets increasingly depend on technology to rep travail done. ITIL 4 moreover emphasizes customer remarks, since it’s less complicated than ever for businesses to consume note their public belief, consumer delight and dissatisfaction.

    For more guidance on the benefits of the newest version of ITIL, behold “ITIL 4: ITSM receives agile.”

    How attain I allot ITIL into follow?

    ITIL is a group of e-books, however in simple terms happening a analyzing binge may not extend your IT operations. First, you should wrap your reason across the ideas and then rep carcass of workers purchase-in. Getting some IT personnel to undertake original strategies can moreover be fancy herding cats, however there are tools that can help.

    along with the ITIL comes an entire suite of consulting, working towards and certification functions. From the early Nineties, certifications were administered by route of two independent bodies: EXIN and ISEB, counting on your area. the two bodies formed an alliance on the conclude of 2006 to additional IT carrier administration.

    because 2014, Axelos is the proprietor of the ITIL personnel certification and checks are administered with the aid of accredited training agencies (ATOs). Accreditations are administered through Strategic Examination Institutes (EIs). EIs should be authorised without detain by using Axelos so as to tender accreditation to ATOs.

    earlier than enforcing ITIL at your companies, there are a couple of questions be sure you reply, similar to what complications your corporation is trying to remedy and what's your route to continual service growth.

    For a deeper peruse at inserting ITIL into follow, behold "7 questions to quiz before implementing ITIL" and "the route to rep began with ITIL."

    what is ITIL certification and is it worth it?

    The ITIL v3 certification scheme in the past consisted of five degrees: foundation, Practitioner, Intermediate, knowledgeable and master. each and every stage required a higher depth of edge and understanding of ITIL. The certification scheme below ITIL four has been streamlined to embrace the ITIL groundwork and the ITIL grasp checks. The ITIL foundation examination has two paths, ITIL Managing professional (MP) or ITIL Strategic chief (SL), which each beget their personal modules and assessments.

    The ITIL Managing skilled (MP) examination is designed for IT practitioners who're involved with know-how and digital teams complete through the firm, no longer simply in the IT department. This route will discipline authorities every exiguous thing they should find out about operating a hit IT tasks, teams and workflows.

    Modules encompass:

  • ITIL specialist – Create, carry and help
  • ITIL specialist – power Stakeholder value
  • ITIL expert – elevated precipitate IT
  • ITIL Strategist – Direct, map & enhance
  • The ITIL Strategic leader (SL) exam is designed for those that contend with “all digitally enabled functions,” and never simply those who topple under IT operations. This direction focuses on how know-how directs enterprise approach and the route IT plays into that.

    Modules consist of:

  • ITIL Strategist – Direct, map & improve
  • ITIL chief – Digital & IT strategy
  • each paths can lead to the ITIL master exam, which is the optimum even of certification which you could achieve with ITIL 4.

    For those already in the hub of working against a ITIL v3 certifications, credit will transfer over to the brand original certifications. Axelos recommends that complete ITIL certification candidates continue the route towards ITIL grasp.

    For in-depth evaluation of ITIL certification, behold "What ITIL certifications imply to your IT management practices."

    How can ITIL better my company's company performance?

    A neatly-run IT company that manages risk and maintains the infrastructure buzzing no longer most efficacious saves cash, but it surely moreover makes it feasible for the commerce people to attain their jobs more with ease. for example, brokerage enterprise Pershing reduced its incident response time via 50 p.c in the first yr after restructuring its carrier desk in line with ITIL guidelines, permitting clients with complications to rep again to travail a lot extra immediately.

    ITIL gives a systematic and professional method to the administration of IT service provision, and presents the following merits:

  • decreased IT charges
  • better IT services by utilizing confirmed most confiscate observe methods
  • improved consumer pride via a extra skilled method to provider delivery
  • necessities and tips
  • stronger productivity
  • more desirable expend of talents and adventure
  • more desirable dawn of third-birthday party services during the specification of ITIL or BS15000 as the common for service delivery in features procurements
  • in response to Axelos, ITIL can additionally assist organizations better functions by using:

  • helping businesses manipulate possibility, disruption and failure
  • strengthening consumer family members with the aid of “providing productive features that meet their needs”
  • setting up most economical practices
  • constructing a accountable environment that soundless permits for boom, scale and alter.
  • For a deeper examine the route to rep essentially the most from ITIL, behold "5 steps to successful ITIL adoption."

    what is going to ITIL charge?

    Getting begun contains the buy of the ITIL both as hardcopy, PDF, ePub or through an online subscription without detain from Axelos. Then there is the cost of training, which fluctuates each yr. The direction leading to the initial basis certificates customarily runs for two days, and classes leading to greater certifications will moreover be a week or extra.

    Add to that the inevitable cost of re-engineering some approaches to conform to ITIL guidelines, and adjustment of assist desk or other application to entangle the counsel you want for tracking and generating metrics.

    there's, by the way, no such aspect as "ITIL-compliant" software; the ITIL is a framework, not a common. Some back desk and administration utility has been engineered with ITIL practices in mind, besides the fact that children, and so will lend themselves more desirable to teams working in the framework.

    Examples of software and services designed with ITIL and ITSM in intellect consist of:

  • Samange: offers provider desk automation with the ITIL framework in mind
  • InvGate provider Desk: a web-based ITIL-ready carrier that boasts a user-pleasant interface
  • ManageEngine ServiceDesk Plus: web-based aid desk and asset management software that's available in an ITIL version
  • vision Helpdesk: A multifunction service desk reply with ITIL integration
  • How lengthy will an ITIL undertaking take?

    ITIL isn't a "challenge"; it's an ongoing adventure to enhance IT service administration. premiere practices should be baked into every exiguous thing, and that they ought to evolve because the commercial enterprise evolves. With IT personnel purchase-in, adjustments can start as soon as team of workers are trained, and some consequences should be obvious within weeks or months. method changes attain consume time, although, as entrenched uncertain practices are rooted out and modified (and, potentially, personnel alterations happen), however many businesses beget suggested giant rate reductions after their first yr.

    To rep a more robust theory of what it'll consume to undertake and invoke ITIL, which you could flick thru case experiences on the Axelos website. recent case experiences encompass businesses fancy Sony and Disney — two corporations with massive IT operations to control.

    What rate reductions can i expect?

    establishments and public sector businesses which beget effectively carried out ITIL superior practices record big rate reductions.

    for example, in its benefits of ITIL paper, crimson Elephant stories that Procter and Gamble saved about $500 million over four years through cutting back assist desk calls and improving operating methods. Nationwide insurance executed a forty % discount in gadget outages and estimates a $four.3 million ROI over three years, and Capital One reduced its "enterprise crucial" incidents via ninety two % over two years. After three years of ITIL implementation, woodland products enterprise MeadWestvaco claimed to beget eradicated more than $one hundred,000 annually in IT preservation contracts and diagnosed a ten p.c profit in operational steadiness thanks to ITIL.

    without purchase-in and cooperation from IT staff, besides the fact that children, any implementation is bound to fail. Bringing most excellent practices into a firm is as plenty a PR job as it is a technical undertaking.

    other criticisms consist of the proven fact that it’s impossible to plot for every failure, adventure or incident so it’s not an accurate science. basically, you gained’t comprehend the accurate ROI on ITIL unless you allot in obligate it inside your firm and expend it with no trouble. in the end, when you deem that ITIL is a framework, it could possibly best be as a success as corporate buy-in makes it feasible for. Embracing certifications, practicing and investing in the shift will back extend the possibilities of success and savings.

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    Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals | existent questions and Pass4sure dumps

    A plastic map for organic synthesis

    The infrastructure for chemical synthesis typically lies at either conclude of a spectrum: small-scale studies in ad hoc assemblies of glassware or large-scale production in capital-intensive custom reactors. Kitson et al. report a hybrid protocol that customizes a blueprint for synthesis of a target compound in a series of interconnected plastic modules, which can be assembled en masse by 3D printing (see the Perspective by Hornung). The approach, demonstrated for the commercial muscle relaxant baclofen, establishes a systematic workflow that is potentially amenable to automation: complete that is necessary for synthesis and purification is the introduction of stock solutions and variation of temperature or pressure.

    Science, this issue p. 314; behold moreover p. 273


    Chemical manufacturing is often done at big facilities that require a sizable capital investment and then produce key compounds for a finite period. They present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in eddy guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. They demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the route for the local manufacture of drugs outside of specialist facilities.

    The manufacture of dynamic pharmaceutical ingredients (APIs) is vital for modern health care, yet faultfinding drugs are regularly manufactured for a finite age in a limited number of sites. The manufacture of chemical products—whether bulk, fine, or specialty chemicals, such as APIs—is currently based on a model whereby a central plant is exclusively designed for the manufacture of the product, or sweep of products, sold by that particular company (1). This model holds whether the manufacturer is a big pharmaceutical company or, as is increasingly the case, a constrict research organization operating big chemical manufacturing plants to order from the pharmaceutical industry. This process leads to safety issues around both the storage and transport of such materials, as well as the issues inherent in the large-scale manufacture of chemicals (2). In addition, these large-scale plants are often at the mercy of complicated and global supply chains of raw materials, the failure of which at any point will reduce or halt the capacity of the plant to produce materials and deliver them effectively (3, 4). Also, when a given involved intermediate or API goes out of production, the plants are often repurposed and the manufacturing capacity is lost. The reinstatement of the process would require, in the best case, substantial capital investment to reconfigure a chemical plant for its synthesis. To alleviate this issue, they pose a concept whereby the large-scale manufacturing process of involved fine chemicals, such as APIs, is augmented by distributed, point-of-use manufacturing in self-contained cartridges, requiring limited user interaction to produce the desired products on demand. To achieve this, they developed a methodology for the translation of bench-scale synthesis procedures into a step-by-step workflow that could be used to create digital designs for custom reactionware that can be fabricated by using three-dimensional (3D) printing technologies. In this way, they direct to stagger beyond the preserve of industrial manufacturing and prototyping applications (5), to revolutionize the relationship between the design, manufacture, and operation of functional devices (6–11) and exploit the increasing expend of 3D printing in the automation of the chemical sciences (12–15). This methodology, which is in stark contrast to both large- and medium-scale traditional chemical manufacture, and moreover to the expend of continuous-flow and microreactor approaches (1, 16, 17), allows for the distribution of simple chemical precursors and solvents rather than the involved products themselves. These precursors could then continue to benefit from the economies of scale brought by traditional manufacturing processes while involved products with short shelf lives, or lower and more distributed demand, can be produced locally. This has added benefits in terms of manufacture of the final products as the synthesis of smaller quantities is inherently safer than large-scale processes and poses less risk to both operators and infrastructure. Further, the translation of these synthetic approaches into a digitally defined format, where the reactor design and, eventually, an automated synthesis procedure are encoded, could allow the digitization of complete chemical products into a very low-cost manufacturing format. This could allow big numbers of discontinued APIs to be made available as they can be brought back into production on a petite scale by the fabrication and expend of the confiscate cartridges (18, 19).

    As a proof of principle, they present a process by which the traditional laboratory-scale synthesis of a commercially available API can be translated into the design of an integrated cartridge. To attain this, complete the reaction steps and intrasynthesis purification processes are encoded into the 3D architecture of the cartridge so that the chemical reactions, work-ups, and purification are done with minimal user intervention and exposure automatically. They beget demonstrated this process in the complete synthesis of the anticonvulsant medication (±)-baclofen (see below).

    This method for translating traditional laboratory syntheses into a figure that can be encapsulated in a sole cartridge is split into three layers of consideration, which were iteratively reevaluated during the cartridge development process. The first is the “conceptual layer,” where the chemical reactions and processes necessary are identified and developed. The second is the “digital layer,” in which these processes are translated into digital 3D models of the final cartridge devices. Finally, a “physical layer,” where the digital models are realized as either a modular implementation or a monolithic implementation, is used to generate the finalized cartridge, which can be used to outcome the designed synthesis (Fig. 1). These physical systems can then be tested for efficacy as a final implementation, before iterating the process to develop accountable cartridge syntheses.

    Fig. 1 Schematic representation of the translation of a multistep synthesis from conception through to implementation as a reaction cartridge.

    Reactions necessary for the synthesis are identified (A→B→C→D, top left panel) and the specific chemical and physical processes and reaction parameters necessary for each reaction are laid out (conditions i. – iii., left panel). These processes are then translated into bespoke reaction modules designed to accomplish one or more of the chemical processes identified in the previous step (top perquisite panel). The modules are then designed as 3D CAD models (lower hub panel), with libraries of module components to accommodate the required reaction parameters. These digital models can then be fabricated to produce either a modular or monolithic implementation (lower perquisite panel) of the process.

    First, the fundamental chemistry required for the transformations is considered and optimized to minimize the necessary interstep purification for the completion of the complete synthesis. This approach is similar to that taken to develop telescoped (i.e., consecutive transformations in a sole reactor or sequence of reactors without isolation and purification of intermediates) and “one-pot” syntheses (20, 21), often used in process chemistry, both of which direct to maximize the efficiency of the synthetic route. Although here it is not necessary to produce genuinely telescoped syntheses, as modules for interstep purification can be built into the cartridge design, the synthesis of the desired compound, including complete reagents and starting materials for complete the necessary steps, must be considered as a unified process. The choice of synthetic route to any target compound will be dictated by a number of factors, including the relative availability and cost of starting materials, reagents, and solvents, as well as the compatibility of reaction and purification sequences with the reactor modules produced. In any wide-scale application of their approach, a cost analysis of any proposed synthetic route will beget to be performed to ensure its viability for the product. Once the chemistry for the synthesis is developed, a sequence can be produced where the physical processes and reaction parameters—such as heating, cooling, phase separations, reaction volumes, and times—can be identified.

    Vital to the success of these modules is the compatibility of the cartridge material with the chemistry being performed. Whereas traditional laboratory syntheses consume space mostly in glassware, they expend polypropylene (PP) as a basic structural material for the fabrication of the cartridges. They beget organize that this polyolefinic material, while demonstrating a robust sweep of chemical compatibility for traditional synthetic organic reactions, is moreover a suitable substrate for 3D printing applications (22–24). This gives the best poise of chemical resistance and material properties for 3D printing. Therefore, the first step in the design process is testing the reactions necessary for compatibility in the reactor materials. Future iterations of the concept could expand on the materials and fabrication processes available for the reaction modules to further develop the sweep of chemistries feasible in this system, using, for example, perfluorinated polymers to extend the chemical resistance of the module.

    To demonstrate the feasibility of incorporating these PP reactors into the production of APIs, they tested a number of reactions that lead to such targets in test modules fabricated from PP (Fig. 2). They tested reactions for the synthesis of three APIs: the central nervous system inhibitor (±)-baclofen (25), the anticonvulsant lamotrigine (26), and the gastroprotective agent zolimidine (27). As can be seen, complete of the reactions tested were observed to work, but with slightly lower efficiency in PP reactors than in traditional glass reactors, owing to physical loss of material on the relatively rugged PP surface hampering product recovery. Surface roughness is inherent in the 3D printed process; however, expend of other, as yet undeveloped, materials or different manufacturing techniques could reduce this issue. The zolimidine reactions, particularly the copper-catalyzed iodination reaction, experienced a pronounced reduction in efficiency, compared to (±)-baclofen or lamotrigine. They surmised that this was due to side reactions of the iodine with the polypropylene. These issues highlight that the process of translation from glassware must consume into account both the physical and chemical properties and limitations of the reactor substrate (23). For this reason, the first two syntheses were selected for further development into reaction cartridges to explore the concept.

    Fig. 2 Comparison of glass reactors with plastic reactionware for the optimized synthetic routes to (±)-baclofen (top), lamotrigine (middle), and zolimidine (bottom) with reaction yields for each step (reaction yields in PP vessels given in parentheses).

    Single (top right) or double (bottom right) chambered polypropylene reaction test cartridges were used. PP, polypropylene; TBAF, tetrabutylammonium fluoride; THF, tetrahydrofuran.

    Once the processes needed for the reaction sequence are identified, the combined continuous protocol is mapped onto the 3D digital designs for the target-specific cartridge. The sequence of processes is split into a series of modules, with each representing a telescoped series of processes that can consume space in a sole chamber of the 3D printed system. Each process module is then created as a digital model that can be manipulated to provide the correct physical dimensions necessary for the reaction scheme. The 3D models of the cartridges used in this study were created with OpenSCAD software, an open-source framework for CSG (constructive solid geometry) modeling that allows a highly springy and configurable approach to create multifarious libraries of components as reusable pieces of code. Once defined, these pieces of code can be manipulated by the software, allowing the generation of involved reactor geometries with minimal human inputs. For example, in this study, they designed a module library consisting of interchangeable top and bottom components with varying features that can be easily combined to produce reaction vessels with different shapes and features. From a sole line of code, an entire module can be created, with 18 different shapes available (i.e., three different tops and six different bottoms can be selected; Fig. 3). The modules were designed around simple chambers where each reaction or process could be performed in as nigh a manner as feasible to the route it would be carried out with traditional batch chemical techniques, easing the transition between published synthesis in glassware and “cartridge” synthesis. Typically, a yardstick module would beget an opening on the top of the wall of the chamber for transfer of reaction mixtures from previous modules and an opening at the bottom of the chamber for expelling material from the module subsequent to the completion of the desired process. The transfer of material between modules is facilitated by a further opening in the roof of the compartment, which can be used to apply pressure that forces the reaction medium out of the chamber via the outlet at the bottom. The opening at the top otherwise equalizes pressure throughout the device to forestall the premature transfer of material, and moreover allows for application of vacuum to remove and exchange solvents. These modules can then be combined in sequences by expend of further components of their module library such as siphon tubes for the transfer of material from one reaction module to another.

    Fig. 3 Parameterized approach to the design of individual process modules.

    Digital libraries of module components (top) can be easily assembled to produce a wide sweep of module geometries dictated by the specific process and reaction parameters (e.g., solvent volumes, number of inputs and outputs, etc.) (bottom). Hydrophobic filters for phase separation are shown in red, and fritted glass filters are shown in blue. DCM, dichloromethane. HR, reactor height.

    Once a reaction chamber is created, original features can be introduced by subtracting or adding shapes to the module. For example, a filtration device can be made from a module with a top input, a round bottom with a port, and a glass filter. To achieve this feature, a cylindrical model conforming to the dimensions of the physical filter to be inserted is created and subsequently subtracted from the model of a reaction chamber, producing a void space in the model into which the filter fits (see supplementary materials). phase separation modules were achieved in a similar manner by using hydrophobic frit inserts that effectively sever organic and aqueous phases for product extractions. In keeping with their crave to design synthesis cartridges that can be produced outside traditional manufacturing regimes, they beget exploited their group’s development of 3D printed reactors—reactionware—for synthetic chemical applications as a method of prototyping the physical reactors (28, 29). Three-dimensional printing–based fabrication approaches beget the added edge of being intimately linked to the design process.

    Fabrication of the modular system was carried out on low-cost (~$2000) 3D printers, Ultimaker 2 and 2+, although many other fused deposition modeling (FDM) printers could print the 3D modules produced through this approach. If it is necessary to incorporate nonprinted materials during 3D printing of the final module, a preprogrammed intermission in the printing process is instigated at a point just above the designed void, and the component is inserted in this space before the resumption of printing. Upon completion of printing, the inlet and outlet ports were tapped with a ¼ inch unified national fine (UNF) thread to allow ease of integration with the external infrastructure for performing the reaction sequences. Using yardstick ports allowed us to attach either yardstick fluidic tubing connectors such as those organize in traditional rush synthesis setups, or widely used Luer lock adapters. These Luer lock connectors are easily reconfigurable, facilitating feedback into the design process.

    The API chosen to accomplish a complete end-to-end synthesis was the central nervous system depressant and antispastic medication (±)-baclofen (30, 31) [RS-β-(4-chlorophenyl)-γ-aminobutyric acid] (4) (Fig. 4), a derivative of γ-aminobutyric acid (GABA) that modulates the action of this central inhibitory neurotransmitter (25). This target was chosen as an instance to demonstrate that even relatively short syntheses require a disproportionately larger set of chemical processing steps to outcome the complete synthesis; in the future, they envision that the synthesis of larger numbers of compounds and compound classes will greatly expand the scope of this approach. (±)-Baclofen has organize a number of applications since its first reported synthesis and is currently being investigated beyond its traditional use, as a high-dose treatment for alcoholism (32). Many syntheses of (±)-baclofen beget been published since it was first reported, often proceeding through the formation, and subsequent hydrolysis, of β-(4-chlorophenyl)-γ-butyrolactam (3). They beget modified such a traditional synthesis of (±)-baclofen starting from the commercially available material methyl 4-chloro-cinammate (1), and proceeding via the Michael addition of nitromethane to figure 4-nitro-3-(4-chlorophenyl)butanoic acid (2), followed by nickel-catalyzed reductive lactamization and subsequent acid hydrolysis to produce the final product in its commercially available racemic figure as a hydrochloride salt. This three–reaction-step sequence contains 12 individual processing steps that must be incorporated into the reactionware device to complete the synthesis (Fig. 4). This sequence was designed to be particularly amenable to translation into the modular or monolithic system as at each stage, the reactions are either sufficiently clean, or reaction impurities that would impinge on subsequent process in the synthesis could be readily removed by phase partition. The final product is purified through a methanol–diethyl ether crystallization, which yields a crystalline solid that can be retrieved directly from the cartridge device. An animation of the entire process, showing the passage of reagents, processes, and work-ups, is shown in movie S1.

    Fig. 4 Synthesis of (±)-baclofen in a series reaction cartridges.

    (Top) Conceptual synthetic procedure for the synthesis of (±)-baclofen under the conditions described in Fig. 2, showing the necessary processing sequence to outcome this synthetic pathway. These processes were then split into modules (a) to (e) (indicated by gray boxes in the process sequences), which they translated into a digital design (middle left) and finally fabricated as either a modular (middle right) or monolithic (bottom left) implementation. A partially fabricated monolithic cartridge is moreover shown indicating the placement of non-3D printed components and internal fluidic pathways (bottom hub and right). Both modular and monolithic cartridges are shown with Luer taper–compatible valving for interfacing with external fluidic inputs and pressure or vacuum lines.

    Each of these processes was translated into operations that could be successfully embodied in one or more reaction or purification modules. The specific reaction modules used for the synthesis of (±)-baclofen were (a) a combined Michael addition, evaporation and ether extraction module; (b) a combined solvent exchange and reduction module; (c) a phase separation and filtration module; (d) a combined solvent exchange and hydrolysis module; and (e) a filtration module. Individual modules were fabricated for a “plug-and-play” approach to the reaction process development by using Luer lock fittings to connect individual modules and Luer taper–compatible valves to interface with pressure or vacuum systems. This design allowed testing of each individual process in isolation before the modules were combined to build up the complete synthesis. Finally, the module designs were “digitally stitched together” by using the developed CAD libraries for internal fluidic pathways to create the design for a monolithic synthesis cartridge. Once fabricated, the individual modules and the monolithic cartridges were evacuated and filled with a nitrogen atmosphere to ensure an inert environment for the subsequent chemistry.

    The first chamber, (a), consists of a lower volume (4.9 ml) where the initial reaction can consume space and is separated from the upper outlet by a hydrophobic frit. Reactor modules (b) and (d) consist of a sole unbroken reaction chamber (31.8 ml) with sufficient volume to accommodate the reaction volumes and extraction solvents from the previous processes before concentration under reduced pressure. Extraction module (c) consists of a chamber of sufficient volume (4.7 ml) to hold the aqueous phase from the previous chamber, which has a drain at the bottom covered by a hydrophobic frit that prevents both solid material and aqueous solution from passing into the next chamber or module. The final module is a filtration module for separating and retrieving the final product. This sole module can be either open to the atmosphere or enclosed as required. During the fabrication process, chambers or modules that required stirring were equipped with a PTFE (polytetrafluoroethylene)–coated magnetic stirring bead (length 10 mm) to enable mixing of the contents. Each module or chamber of the monolith was equipped with a ¼ inch UNF threaded port carrying a female Luer lock adapter, which was used to interpolate an inert (dry, N2) atmosphere, or reduced pressure, into the system. The modular system was designed such that there was a sole fluidic path through the reactor; rush from one chamber into the next was induced either by pressure from excess solvent, in the case of the phase separation processes, or the introduction of nitrogen pressure distinction between the apropos chambers to shove the reaction compund through an embedded channel running from the bottom of one chamber to the top of the next.

    Starting materials were prepared as simple solutions and transferred to the cartridge via yardstick Luer syringes. The cooling and heating required for the reaction sequence were achieved by the immersion of the reaction cartridge or module in an ice or sand bath, respectively, and the temperature required for the reactions can be achieved automatically on a stirring-hotplate. The exact sequence of operations, positioning of the module in the heating or cooling bath, and time intervals necessary for completing the synthesis are outlined in the supplementary materials (figs. S12 and S13 and table S3).

    Performing the synthesis starting from 200 mg of 1 in the manner described yielded 98 mg (39% yield over three reaction steps and 12 processing steps from 1 with ≥95% purity as determined by high-performance liquid chromatography) of (±)-baclofen hydrochloride salt, which is more than 1 day’s maximum dosage of the drug. Better efficiency of reaction can be achieved with lower concentrations of starting materials (using a similar cartridge at half concentration, i.e., 100-mg scale, gave a 44% yield over three steps of similar purity). Increasing the volume of the reactor as well increases the quantity of (±)-baclofen obtained [a 300-mg scale synthesis yielded 133 mg (35%) (±)-baclofen]. The integration of the reaction processing steps into the design of the modules greatly simplifies the operations required to perform the reaction sequence compared to traditional bench synthesis and simultaneously reduces the even of technical skills required to perform the process down to simple operations that attain not require the specific skills of a trained synthetic chemist. Although the total time for the reaction sequence is around 40 hours in this case, including complete intermediate operations, the workflow is constrained by the geometry of the device, so complete human interaction is limited to simple interventions at specific time periods, and it should be feasible to abbreviate the interaction time further. The expend of such bespoke, single-use cartridges would greatly reduce the time spent on glassware preparation, liquid handling, and other ancillary tasks associated with the majority of chemical syntheses at this scale. Also, by using the geometry of the reactor to constrain the operation of the synthesis, they reduce the human decision making involved in the synthesis processes, making the sequence more reproducible. Given sufficient facilities, several instances of the synthesis cartridge could be used at once, achieving scalability by numbering-up arrays of cartridges, and using these in parallel to extend the output. As a result of the capacity to parameterize and encode multistep organic synthesis reactions with work-ups embedded, they envisage that a digital programmable universal heater-stirrer-solvent-reagent plug-and-play device can be constructed into which only the cartridge, specific to a given synthesis, can be plugged in.

    The (±)-baclofen synthesis necessitated liquid handling and separation of reaction chambers to outcome the complete reaction sequence. In some cases, however, syntheses can be conducted in sole reaction cartridges, depending on the nature and character of the interstep purification required. For example, the synthesis of lamotrigine (Fig. 2) can be achieved in a sole cartridge as the intermediate material is insoluble in the reaction solvent at low temperatures. In a single, closed, filtration module, the initial reaction product could be washed and processed in situ before introduction of the solvent for the subsequent cyclization step. This stands in contrast to the traditional procedure, which requires the solid product of the first step to be removed from the initial reactor to be filtered, dried, and then reintroduced to a reactor for the second step of the synthesis. Performing the synthesis of lamotrigine on a 250-mg scale of starting material yields 112 mg (46% over two reaction steps) of the final product, giving an off-white crystalline powder.

    The digital approach to the design of the system that they beget adopted allows the blueprints for these cartridges to be stored electronically for implementation as and when required. The distribution model for fine and specialty chemicals, such as the APIs implied by this approach, would lead to a decentralizing of logistical approaches to chemical manufacture. Here, any location with access to a sufficiently diverse market of chemical precursors and suitable cartridge fabrication facilities could be used to produce chemical products, which could previously be achieved only in a fully equipped synthesis laboratory with highly trained staff. This approach not only holds pledge for eventually delivering on-demand personalized medicines manufactured at, or near, the point of use, but moreover has short-term potential applications in the synthesis of APIs that are currently out of production. An immediate impact of digitization is that the cost for synthesis at the bench scale (milligrams) could dwindle markedly owing to savings in labor and infrastructure with only a one-off digitization cost (and allow operators to manufacture 5 to 10 different products at the same time). Once the saving meets the digitization cost, the efforts of the expert chemist will shift from bespoke on-demand chemical manufacturing to chemical digitization (see supplementary materials for an economic analysis). Their methodology will beget the most rapid impact for chemicals that are currently produced on require in petite batches and that occupy a gap in the market where the require for a product is sufficient for it to be commercially viable but insufficient to justify plant-scale production. This gap lies between the elevated cost of bench-scale versus reactor-scale synthesis, and thus the digitization benefit of compounds in this zone is high.

    The regulatory framework necessary to produce involved materials in this mode will necessity thorough attention; indeed, their approach would require a completely original system for the regulation of API manufacture. This system would beget to be developed alongside the evolution of this approach as a method for pharmaceutical synthesis, which they beget presented here in proof-of-concept form; however, they can envision a situation in which regulatory agencies certify specific cartridge or module designs as soon as a digitized process is fully established (including the embedded quality-control protocols), independent of the physical location of person who uses the cartridge. This approach has multiple benefits. First, the framework can adopt well-established methods of digital remonstrate certification from the information technology universe (e.g., digital signing with asymmetric ciphers). Second, no explicit certification would be needed for each original “facility” (which might be a hospital or a private house) that would necessity the drug. Third, existing methods for protecting and manipulating digital content provide much more efficient models for distribution and regulation compared to the retail and patent system, respectively. These regulatory issues surrounding the commercial or clinical application of this approach are not trivial, and faith must be taken to ensure that end-user safety is not compromised. However, they believe that the benefits in terms of efficiency of delivery, robustness of supply, and sweep of materials available could lead to the digitization of chemical synthesis.

    Acknowledgments: They confess the succor of S. Marshall in compiling their analysis of the economic impact of their methodology. Supplementary materials embrace a PDF document detailing the materials and methods used in this article; the STL and OpenSCAD files used to generate complete 3D printed objects mentioned; a schematic movie illustrating the process of baclofen synthesis in the monolithic cartridge; and Python code that can be used to automate the stirrer-hotplate operations for the baclofen synthesis. They gratefully confess financial back from the Engineering and Physical Sciences Research Council (grant nos. EP/H024107/1, EP/J015156/1, EP/K021966/1, EP/L015668/1, EP/L023652/1) and European Research Council (project 670467 SMART-POM). This research was developed with funding from the Defense Advanced Research Projects Agency (DARPA). The views, opinions and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. L.C. is the founder and director of CroninGroupPLC and is listed as an inventor on a patent application filed by The University of Glasgow (GB 1800299.8). L.C. conceived the initial concept and the design approach; P.J.K. designed the reactionware with succor from J.P.F. and S.Z.; G.M. and R.C.S. telescoped the methods, porting them from glass to plastic; and P.J.K. developed the monolithic cartridges with succor from S.Z. J.S.M. helped evaluate the purity of the products, and P.J.K. coordinated the team with succor from L.C.

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  • Count Your Steps While Walking
  • Getting set up is a exiguous tricky, but, don’t worry, I’ll walk you through it. And if you beget any problems you can quiz for succor through the discussion forum. I’ll explain an facile method to enable and acquire data from complete 5 iOS sensors including:

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  • Angular Velocity Sensors — Detect your iPhone’s movement and expend to control software
  • Position Sensors — Capture your GPS position and precipitate and build location based apps
  • You will learn how facile it is to enable these sensors and acquire data for your MATLAB programs.

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    By Nigel Slack, Alistair Jones
    Publisher : Pearson (Feb 2018)
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