American National Standard N537 : radiological safety standard for the design of radiographic and fluoroscopic industrial x-ray equipment /

"ANSI N537-1976."

Colloquium on Regulatory Design in Theory and Practice. Washington, D.C., 1984-1985 /

"September, 1985"--P. 3.

Residential treatment for the disturbed child: basic principles in planning and design of programs and facilities.

Includes index.

Sharpe's London magazine of entertainment and instruction for general reading

Mode of access: Internet.

Design, Synthesis, Potency and Cytoselectivity of Anticancer Agents Derived by Parallel Synthesis from alpha-Aminosuberic Acid

Chemotherapy in the last century was characterized by cytotoxic drugs that did not discriminate between cancerous and normal cell types and were consequently accompanied by toxic side effects that were often dose limiting. The ability of differentiating agents to selectively kill cancer cells or transform them to a nonproliferating or normal phenotype could lead to cell- and tissue-specific drugs without the side effects of current cancer chemotherapeutics. This may be possible for a new generation of histone deacetylase inhibitors derived from amino acids. Structure-activity relationships are now reported for 43 compounds derived from 2-aminosuberic acid that kill a range of cancer cells, 26 being potent cytotoxins against MM96L melanoma cells (IC50 20 nM-1 mu M), while 17 were between 5- and 60-fold more selective in killing MM96L melanoma cells versus normal (neonatal foreskin fibroblasts, NFF) cells. This represents a 10- to 100-fold increase in potency and up to a 10-fold higher selectivity over previously reported compounds derived from cysteine (J. Med. Chem. 2004, 47, 2984). Selectivity is also an underestimate, because the normal cells, NFF, are rarely all killed by the drugs that also induce selective blockade of the cell cycle for normal but not cancer cells. Selected compounds were tested against a panel of human cancer cell lines (melanomas, prostate, breast, ovarian, cervical, lung, and colon) and found to be both selective and potent cytotoxins (IC50 20 nM-1 mu M). Compounds in this class typically inhibit human histone deacetylases, as evidenced by hyperacetylation of histones in both normal and cancer cells, induce expression of p21, and differentiate surviving cancer cells to a nonproliferating phenotype. These compounds may be valuable leads for the development of new chemotherapeutic agents.

Accommodating intraocular lenses:a review of design concepts, usage and assessment methods

The correction of presbyopia and restoration of true accommodative function to the ageing eye is the focus of much ongoing research and clinical work. A range of accommodating intraocular lenses (AIOLs) implanted during cataract surgery has been developed and they are designed to change either their position or shape in response to ciliary muscle contraction to generate an increase in dioptric power. Two main design concepts exist. First, axial shift concepts rely on anterior axial movement of one or two optics creating accommodative ability. Second, curvature change designs are designed to provide significant amplitudes of accommodation with little physical displacement. Single-optic devices have been used most widely, although the true accommodative ability provided by forward shift of the optic appears limited and recent findings indicate that alternative factors such as flexing of the optic to alter ocular aberrations may be responsible for the enhanced near vision reported in published studies. Techniques for analysing the performance of AIOLs have not been standardised and clinical studies have reported findings using a wide range of both subjective and objective methods, making it difficult to gauge the success of these implants. There is a need for longitudinal studies using objective methods to assess long-term performance of AIOLs and to determine if true accommodation is restored by the designs available. While dual-optic and curvature change IOLs are designed to provide greater amplitudes of accommodation than is possible with single-optic devices, several of these implants are in the early stages of development and require significant further work before human use is possible. A number of challenges remain and must be addressed before the ultimate goal of restoring youthful levels of accommodation to the presbyopic eye can be achieved.

Improved production of industrially relevant recombinant proteins: application of multi-factorial design of experiments and scalable process modelling

The work described in this thesis focuses on the use of a design-of-experiments approach in a multi-well mini-bioreactor to enable the rapid establishments of high yielding production phase conditions in yeast, which is an increasingly popular host system in both academic and industrial laboratories. Using green fluorescent protein secreted from the yeast, Pichia pastoris, a scalable predictive model of protein yield per cell was derived from 13 sets of conditions each with three factors (temperature, pH and dissolved oxygen) at 3 levels and was directly transferable to a 7 L bioreactor. This was in clear contrast to the situation in shake flasks, where the process parameters cannot be tightly controlled. By further optimisating both the accumulation of cell density in batch and improving the fed-batch induction regime, additional yield improvement was found to be additive to the per cell yield of the model. A separate study also demonstrated that improving biomass improved product yield in a second yeast species, Saccharomyces cerevisiae. Investigations of cell wall hydrophobicity in high cell density P. pastoris cultures indicated that cell wall hydrophobin (protein) compositional changes with growth phase becoming more hydrophobic in log growth than in lag or stationary phases. This is possibly due to an increased occurrence of proteins associated with cell division. Finally, the modelling approach was validated in mammalian cells, showing its flexibility and robustness. In summary, the strategy presented in this thesis has the benefit of reducing process development time in recombinant protein production, directly from bench to bioreactor.

The influence of twist drill design on rigidity and chip disposal

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Online-questionnaire design:establishing guidelines and evaluating existing eupport

As a new medium for questionnaire delivery, the internet has the potential to revolutionise the survey process. Online (web-based) questionnaires provide several advantages over traditional survey methods in terms of cost, speed, appearance, flexibility, functionality, and usability [1, 2]. For instance, delivery is faster, responses are received more quickly, and data collection can be automated or accelerated [1- 3]. Online-questionnaires can also provide many capabilities not found in traditional paper-based questionnaires: they can include pop-up instructions and error messages; they can incorporate links; and it is possible to encode difficult skip patterns making such patterns virtually invisible to respondents. Like many new technologies, however, online-questionnaires face criticism despite their advantages. Typically, such criticisms focus on the vulnerability of online-questionnaires to the four standard survey error types: namely, coverage, non-response, sampling, and measurement errors. Although, like all survey errors, coverage error (“the result of not allowing all members of the survey population to have an equal or nonzero chance of being sampled for participation in a survey” [2, pg. 9]) also affects traditional survey methods, it is currently exacerbated in online-questionnaires as a result of the digital divide. That said, many developed countries have reported substantial increases in computer and internet access and/or are targeting this as part of their immediate infrastructural development [4, 5]. Indicating that familiarity with information technologies is increasing, these trends suggest that coverage error will rapidly diminish to an acceptable level (for the developed world at least) in the near future, and in so doing, positively reinforce the advantages of online-questionnaire delivery. The second error type – the non-response error – occurs when individuals fail to respond to the invitation to participate in a survey or abandon a questionnaire before it is completed. Given today’s societal trend towards self-administration [2] the former is inevitable, irrespective of delivery mechanism. Conversely, non-response as a consequence of questionnaire abandonment can be relatively easily addressed. Unlike traditional questionnaires, the delivery mechanism for online-questionnaires makes estimation of questionnaire length and time required for completion difficult1, thus increasing the likelihood of abandonment. By incorporating a range of features into the design of an online questionnaire, it is possible to facilitate such estimation – and indeed, to provide respondents with context sensitive assistance during the response process – and thereby reduce abandonment while eliciting feelings of accomplishment [6]. For online-questionnaires, sampling error (“the result of attempting to survey only some, and not all, of the units in the survey population” [2, pg. 9]) can arise when all but a small portion of the anticipated respondent set is alienated (and so fails to respond) as a result of, for example, disregard for varying connection speeds, bandwidth limitations, browser configurations, monitors, hardware, and user requirements during the questionnaire design process. Similarly, measurement errors (“the result of poor question wording or questions being presented in such a way that inaccurate or uninterpretable answers are obtained” [2, pg. 11]) will lead to respondents becoming confused and frustrated. Sampling, measurement, and non-response errors are likely to occur when an online-questionnaire is poorly designed. Individuals will answer questions incorrectly, abandon questionnaires, and may ultimately refuse to participate in future surveys; thus, the benefit of online questionnaire delivery will not be fully realized. To prevent errors of this kind2, and their consequences, it is extremely important that practical, comprehensive guidelines exist for the design of online questionnaires. Many design guidelines exist for paper-based questionnaire design (e.g. [7-14]); the same is not true for the design of online questionnaires [2, 15, 16]. The research presented in this paper is a first attempt to address this discrepancy. Section 2 describes the derivation of a comprehensive set of guidelines for the design of online-questionnaires and briefly (given space restrictions) outlines the essence of the guidelines themselves. Although online-questionnaires reduce traditional delivery costs (e.g. paper, mail out, and data entry), set up costs can be high given the need to either adopt and acquire training in questionnaire development software or secure the services of a web developer. Neither approach, however, guarantees a good questionnaire (often because the person designing the questionnaire lacks relevant knowledge in questionnaire design). Drawing on existing software evaluation techniques [17, 18], we assessed the extent to which current questionnaire development applications support our guidelines; Section 3 describes the framework used for the evaluation, and Section 4 discusses our findings. Finally, Section 5 concludes with a discussion of further work.