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Absolute novelty is adopted by most countries depression chemical imbalance test best anafranil 50mg, meaning that which has not been disclosed anywhere in the world job depression test buy anafranil 25 mg amex. Some countries have legal provisions accepting the disclosure of the innovation before seeking protection anxiety chest pains cheap anafranil 25mg overnight delivery, as long as the patent application is filed within a reasonable period that is predefined in law mood disorder centre hong kong cheap anafranil 10mg overnight delivery. In spite of the positive aspect conferred by the grace period, it must be noted that not all countries accept this provision or similar procedures. Therefore, even though this possibility exists in Brazil, the filing in other countries that do not accept previous disclosure (the majority of European countries, for example) can be prejudiced. Hence, even in Brazil disclosure before filing a patent application should be avoided. The latter would only then be the case if the existence of the compound concerned had recognizably been made publicly available'. Inventive step To meet this requirement, an invention may not be obvious in the sense that the idea would not have occurred to a specialist in the field to which the creation pertains if that specialist were called on to find a solution to the problem resolved by the creation. In other words, the matter to be protected cannot be a simple substitution of matters or means known by others who have conceived the same function, nor a mere combination of known means without a new and unexpected technical effect. As an example, suppose that it is known to experts in the field that an extract from the plant Clusia criuva has anti-inflammatory activity. Therefore, a specialist in the subject would be led to test other species of the genus Clusia for the same biological activity (anti-inflammatory). Nevertheless, a way to prove inventive step would be to demonstrate that the species of interest, for example Clusia rosea, presents an unexpected technical effect. In other words, while the species Clusia criuva has an undesirable side effect associated with its anti-inflammatory action, such 380 Animal Cell Technology as harm to the intestinal mucous, Clusia rosea does not have this disadvantage, and thus can meet the requirement of inventive step. The stance of the European Patent Office in general is to consider as indicative of the presence of the inventive step the existence of surprising or superior properties, which could not be anticipated by persons skilled in the art. In the case of a new protein, for instance, this might be fewer or less severe side effects, better absorption, or greater stability. The same reasoning can be applied to the inventive activity involving antigens and antibodies. If the antigen is new and has an inventive step because of surprising properties, then it is patentable. The same goes for a mAb directed against a patentable antigen, since it is new and a person skilled in the art would not have found any suggestion of obtaining it. If on the other hand the antigen (or antiserum) is known, a person skilled in the art would be capable of preparing mAbs against the antigen, without difficulty, based on his or her technical knowledge. A particular mAb will be new in this case, because it has not been described in the state of the art, but will lack an inventive step to the extent that an average specialist in the field could obtain it based on knowledge of the antigen. However, even if an antigen is known, a specific mAb could still show an inventive step as long as it presents a superior property when compared to other antibodies directed against the same antigen. The use of this specific mAb might offer surprising advantages in diagnosing and/or treating a disease caused by the antigen. The selection of this specific mAb, starting from a large number of antibodies aimed against the same antigen, but possessing diverse epitopes, justifies the existence of inventive activity. The surprising technical effect required to establish the presence of an inventive step imposes limits on the possibilities of generalizing the invention, that is, the scope of protection. It should be pointed out that in cases of mAbs, the complex structures of the corresponding genes, which lead to a vast number and variety of antibodies, generally mean it is impossible to isolate a single mAb a second time, so as to satisfy the capacity for repetition. Industrial application An invention must have a use in economic or industrial production. The term ``industrial' is used in the broad sense to cover both products and processes, including any economic activity that involves obtaining products in varied sectors besides industry per se, such as agriculture, fishing, Intellectual property 381 Table 15. In addition to the above three requirements, inventors must also clearly and completely describe the invention. The specification of a patent application must clearly and sufficiently describe the subject matter, so that it can be carried out by a skilled person in the subject. Some countries (such as Brazil and the United States) also require an indication, when applicable, of the best way of executing the invention, called the best mode of the invention. Europe does not have the best-mode requirement in the European Patent Convention, meaning the applicant is not obliged to deposit biological material merely with the intent of allowing reproduction of the invention.

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Nevertheless depression symptoms checklist generic anafranil 75 mg without prescription, it provides a clear illustration of the design of a system using generic operations and a good introduction to depression definition in economy buy discount anafranil 50mg on line the more substantial systems to depression game anafranil 75 mg mastercard be developed later in this chapter depression test boots 10 mg anafranil with mastercard. Addition of complex numbers reduces in this representation to addition of coordinates: Real-part(z 1 + z 2) = Real-part(z 1) + Real-part(z 2), Imaginary-part(z 1 + z 2) = Imaginary-part(z 1) + Imaginary-part(z 2). When multiplying complex numbers, it is more natural to think in terms of representing a complex number in polar form, as a magnitude and an angle (r and A in Figure 2. Yet, from the viewpoint of someone writing a program that uses complex numbers, the principle of data abstraction suggests that all the operations for manipulating complex numbers should be available regardless of which representation is used by the computer. For example, it is oen useful to be able to find the magnitude of a complex number that is specified by rectangular coordinates. Similarly, it is oen useful to be able to determine the real part of a complex number that is specified by polar coordinates. To design such a system, we can follow the same data-abstraction strategy we followed in designing the rational-number package in Section 2. Assume that the operations on complex numbers are implemented in terms of four selectors: real-part, imag-part, magnitude and angle. Also assume that we have two procedures for constructing complex numbers: make-from-real-imag returns a complex number with specified real and imaginary parts, and make-from-mag-ang returns a complex number with specified magnitude and angle. Using these constructors and selectors, we can implement arithmetic on complex numbers using the "abstract data" specified by the constructors and selectors, just as we did for rational numbers in Section 2. As shown in the formulas above, we can add and subtract complex numbers in terms of real and imaginary parts while multiplying and dividing complex numbers in terms of magnitudes and angles: 234 (define (add-complex z1 z2) (make-from-real-imag (+ (real-part z1) (real-part z2)) (+ (imag-part z1) (imag-part z2)))) (define (sub-complex z1 z2) (make-from-real-imag (- (real-part z1) (real-part z2)) (- (imag-part z1) (imag-part z2)))) (define (mul-complex z1 z2) (make-from-mag-ang (* (magnitude z1) (magnitude z2)) (+ (angle z1) (angle z2)))) (define (div-complex z1 z2) (make-from-mag-ang (/ (magnitude z1) (magnitude z2)) (- (angle z1) (angle z2)))) To complete the complex-number package, we must choose a representation and we must implement the constructors and selectors in terms of primitive numbers and primitive list structure. In order to make the different choices concrete, imagine that there are two programmers, Ben Bitdiddle and Alyssa P. Hacker, who are independently designing representations for the complex-number system. With this choice, selecting the real and imaginary parts of a complex number is straightforward, as is constructing a complex number with given real and imaginary parts. To find the magnitude and the angle, or to construct a complex number with a given magnitude and angle, he uses the trigonometric relations x = r cos A, r = x 2 + y2, y = r sin A, A = arctan(y, x), which relate the real and imaginary parts (x, y) to the magnitude and the 235 angle (r, A). For her, selecting the magnitude and angle is straightforward, but she has to use the trigonometric relations to obtain the real and imaginary parts. If both representations are included in a single system, however, we will need some way to distinguish data in polar form from data in rectangular form. A straightforward way to accomplish this distinction is to include a type tag -the symbol rectangular or polar-as part of each complex number. In order to manipulate tagged data, we will assume that we have procedures type-tag and contents that extract from a data object the tag and the actual contents (the polar or rectangular coordinates, in the case of a complex number). We will also postulate a procedure attachtag that takes a tag and contents and produces a tagged data object. A straightforward way to implement this is to use ordinary list structure: (define (attach-tag type-tag contents) (cons type-tag contents)) 237 (define (type-tag datum) (if (pair? In addition, Ben and Alyssa must make sure that the names of their procedures do not conflict. One way to do this is for Ben to append the suffix rectangular to the name of each of his representation procedures and for Alyssa to append polar to the names of hers. In either case, we use contents to extract the bare, untagged datum and send this to the rectangular or polar procedure as required: (define (real-part z) (cond ((rectangular? One reasonable choice is to construct rectangular numbers whenever we have real and imaginary parts and to construct polar numbers whenever we have magnitudes and angles: 240 Programs that use complex numbers add-complex sub-complex mul-complex div-complex Complex-arithmetic package real-part magnitude angle Rectangular representation imag-part Polar representation List structure and primitive machine arithmetic Figure 2. Since each data object is tagged with its type, the selectors operate on the data in a generic manner. Conversely, when Alyssa constructs a number for general use, she tags it with a type so that it can be appropriately recognized by the higher-level procedures. One weakness is that the generic interface procedures (realpart, imag-part, magnitude, and angle) must know about all the different representations. For instance, suppose we wanted to incorporate a new representation for complex numbers into our complex-number system.

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One of the critical parameters that should be evaluated at different scales is the rotation speed of the impeller depression definition science order anafranil 25mg with visa. Different criteria can be employed: to depression with psychotic features generic 75mg anafranil free shipping maintain constant the power per fluid volume dissipated by the impeller; (ii) to anxiety 2 weeks after quitting smoking buy generic anafranil 10 mg keep constant the peripheral velocity of the impeller; (iii) to depression symptoms unemployment buy 10mg anafranil overnight delivery maintain constant the volumetric oxygen transfer coefficient (kL a). Each of these criteria will give different results, so that they should be carefully evaluated, preferably from experimental results. For the aeration parameters, it is important to evaluate which is the most relevant phenomenon; the capacity of bubbles for oxygen transfer or their negative effect on the cells (Chisti, 2000). At very large scales, the ventilation is also a very important issue, mainly if low aeration rates with pure oxygen are used (Gray et al. Since in animal cell culture processes the effects of mechanical stress are much more relevant than in microbial fermentations (Chisti, 1993), it is quite common to adopt scale-up criteria that are associated with cell damage (Joshi et al. When bioreactors coupled to cell retention devices are used, it is also necessary to evaluate the scale-up of the cell separation equipment. In the case of the spin-filter (see Chapter 11), parameters such as filter rotation velocity and the ratio of filtration area to bioreactor working volume are particularly relevant (Deo et al. The complex production facilities required for the cultivation of animal cells, with sophisticated auxiliary services that should avoid contamination and toxicity in the cultures, and fitted with highly automated and validatable equipment, are the reasons why the main cost component of these processes is associated with equipment and other technical components (Petrides, 2000). That is why the main economic consequence of animal cell process optimization is the decrease of the scale of equipment needed to meet a given product demand. Volumetric productivity of a process is a parameter that determines the size of the facilities needed to obtain a given annual production, thus determining the economic efficiency of protein production based on animal cells. This time is a function of the specific growth rate of the cell line and of the inoculation density; tprod ј duration of the production phase. As can be observed from Equations 19 to 22, for an industrial bioreactor with a given volume and operation mode, the volumetric productivity depends basically on cell concentration in the production phase and on the specific product formation rate (qP). The values of qP can vary significantly as a function of the expression system used and of the recombinant protein product. In general, values in the range of 1­30 pg cell­1 day­1 are reported for stably transfected cell lines. However, Chico and Jager (2000) have reported values as high as Ё 85 pg cell­1 day­1 for the expression of a protein using the insect cellbaculovirus expression vector system. This value approaches the maximum theoretical value that is expected for animal cells, which is 100 pg cell­1 day­1 (Ozturk, 1990). In this way, the use of bioreactors that allow high cell density cultures is of great importance as a tool to increase process productivity. Also, it is important to note that as cell concentration increases, the complexity of the process increases and, consequently, bioreactor scale-up becomes limited, for example by physical limitations of materials used in hollow-fiber cartridges. As can be observed, batch and fed-batch cultivations attain dry biomass values comparable to those of continuous cultures of microorganisms, so that mass and heat transfer capacities are not limited for these operation modes. However, high cell density cultivation in heterogeneous bioreactors, such as hollow-fiber devices, reaches dry biomass values similar to the maxima observed in microbial cultures. Application of this equation for volumetric productivities up to 500 mg L­1 d­1 is illustrated in Figure 9. As a result of recent advances in the use of recombinant antibodies for the treatment of chronic diseases and several types of cancer, a growing number of new therapeutic antibodies is currently under development (see Chapters 16 and 17). As a consequence, large investments in the construction of industrial animal cell facilities are being made, surpassing 1 million liters in terms of total installed capacity. However, from the relationship between culture volume and production capacity reported by many companies, it is possible to observe that volumetric productivities lower than 50 mg L­1 d­1 are still quite usual. Bioreactors for animal cells 1000 255 Annual production (kg) 500 100 300 100 50 10 30 10 mg L 1d 1 100 1 1000 10 000 Bioreactor volume (L) 100 000 Figure 9. Thus, it becomes evident that increases in the volumetric productivity up to levels in the range of 500 mg L­1 d­1 could lead to a decrease of one order of magnitude in the culture volume needed to obtain a large amount of therapeutic proteins on an industrial scale. Brucato A, Ciofalo M, Grisafi F, Micale G (1998), Numerical prediction of flow fields 256 Animal Cell Technology in baffled stirred vessels: a comparison of alternative modelling approaches, Chem.

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An editor should give unbiased consideration to anxiety and depression buy 50 mg anafranil otc all manuscripts offered for publication mood disorder 296 generic anafranil 50 mg overnight delivery, judging each on its merits without regard to depression symptoms eating cheap anafranil 10mg on line race depression test hindi cheap anafranil 10mg amex, religion, nationality, sex, seniority, or institutional affiliation of the author(s). An editor may, however, take into account relationships of a manuscript immediately under consideration to others previously or concurrently offered by the same author(s). The sole responsibility for acceptance or rejection of a manuscript rests with the editor. Responsible and prudent exercise of this duty normally requires that the editor seek advice from reviewers, chosen for their expertise and good judgment, as to the quality and reliability of manuscripts submitted for publication. However, manuscripts may be rejected without review if considered inappropriate for the journal. Editorial consideration of the manuscript in any way or form by the author-editor would constitute a conflict of interest, and is therefore improper. The report may be written by the person who discovered the error or by an original author. An author may request that the editor not use certain reviewers in consideration of a manuscript. This might be the case, for example, when a manuscript seriously disagrees with the previous work of a potential reviewer. For critical materials used in the work, proper citation to sources should also be made when these were supplied by a nonauthor. Any unusual hazards inherent in the chemicals, equipment, or procedures used in an investigation should be clearly identified in a manuscript reporting the work. The convenience of readers is served if reports on related studies are published in the same journal, or in a small number of journals. Copies of those manuscripts should be supplied to the editor, and the relationships of such manuscripts to the one submitted should be indicated. It is generally permissible to submit a manuscript for a full paper expanding on a previously published brief preliminary account (a "communication" or "letter") of the same work. However, at the time of submission, the editor should be made aware of the earlier communication, and the preliminary communication should be cited in the manuscript. An author should identify the source of all information quoted or offered, except that which is common knowledge. An experimental or theoretical study may sometimes justify criticism, even severe criticism, of the work of another scientist. Other contributions should be indicated in a footnote or an "Acknowledgments" section. Inasmuch as the reviewing of manuscripts is an essential step in the publication process, and therefore in the operation of the scientific method, every scientist has an obligation to do a fair share of reviewing. If in doubt, the reviewer should return the manuscript promptly without review, advising the editor of the conflict of interest or bias. A reviewer should not evaluate a manuscript authored or coauthored by a person with whom the reviewer has a personal or professional connection if the relationship would bias judgment of the manuscript. It should neither be shown to nor discussed with others except, in special cases, to persons from whom specific advice may be sought; in that event, the identities of those consulted should be disclosed to the editor. Any statement that an observation, derivation, or argument had been previously reported should be accompanied by the relevant citation. Should a reviewer receive a manuscript at a time when circumstances preclude prompt attention to it, the unreviewed manuscript should be returned immediately to the editor. Alternatively, the reviewer might notify the editor of probable delays and propose a revised review date. Reviewers should not use or disclose unpublished information, arguments, or interpretations contained in a manuscript under consideration, except with the consent of the author. A scientist publishing in the popular literature has the same basic obligation to be accurate in reporting observations and unbiased in interpreting them as when publishing in a scientific journal. An account of the experimental work and results that support a public pronouncement should be submitted as quickly as possible for publication in a scientific journal. Scientists should, however, be aware that disclosure of research results in the public press or in an electronic database or bulletin board might be considered by a journal editor as equivalent to a preliminary communication in the scientific literature. Scientists communicate in a variety of ways, but much of the communication is through publication in books and journals. In this chapter, the different types of book and journal presentations are described, along with the components of the standard format for reporting original research.

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