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I should like to set the stage for this meeting by exploring how the concept of probability was transformed by developments in atomic physics during 1913–1927. In outline I will proceed as follows: I will begin with a survey of the visual imagery, causality and probability of classical physics; then I turn to Niels Bohr’s 1913 theory of the atom and the emergence in 1924 of nonclassical notions of probability; the contrast between the quantum and wave mechanics in 1926; Max Born’s theory of scattering; Werner Heisenberg on fluctuations, discontinuity and probability; transformation theory and word meanings; the uncertainty principle paper; and then conclude with Niels Bohr’s concept of complementarity.

Paintings on the walls of caves inhabited by people thousands of years ago (Blakemore, 1988), illuminated manuscripts preserved from the Middle Ages, declarations of love carved on Victorian lace bobbins, the first attempts of four-year-old children to write their names; for thousands of years people have had a strong desire to make their mark, more or less permanently, on paper and other materials.

The purpose of this paper is to summarise the state of Coronavirus epitope research, with an emphasis laid on the most recent achievements, i.e. the correlation between antigenicity and polypeptide primary structure. The antigenic properties of coronaviruses reside mainly in their envelope glycoproteins: the S (spike) protein, a high molecular weight polypeptide which constitutes the petal-shaped peplomers and the M (membrane) protein, a smaller integral membrane polypeptide. Some coronaviruses possess an additional surface glycoprotein, the haemagglutinin-esterase (HE) protein.

The word “evolution” usually evokes thoughts of events which occurred in the distant past, but it is self-evidently an ongoing process. The application of intense selective pressure, for example by the wide-spread use of vaccination, and also the transport of infected animals over large distances may have contributed to what may be considered “short-term” evolution. Papers relevant to putative Coronavirus evolution in both recent and distant time-scales are presented in this volume.

Enveloped viruses carry in their membranes one or more surface glycoproteins. In coronaviruses three such proteins have been identified: a small integral membrane protein (M), a large glycoprotein constituting the characteristic viral spikes (S), and an intermediate-sized glycoprotein (HE). This paper will summarize published knowledge on the properties and function of the small and the intermediate-sized membrane proteins. They will be referred to as M and HE, respectively.

Hydrogels are water-swollen polymer networks. They are of great interest both medically and commerically. Conventional hydrogels change little in swelling with environmental conditions while stimuli-responsive hydrogels may swell or deswell sharply with relatively small changes of temperature or pH. A general review of the principles and applications of these interesting materials is presented here.

Those of us who believe that human welfare is significantly aided by technological progress have a clear motivation to accentuate the positive and to mitigate the negative consequences of technology. We thus share a common objective to allocate our limited societal resources effectively so as to improve public health and safety by minimizing real risks, both present and future.

Virus infections of the central nervous system (CNS) may result in the loss of myelin sheaths without axonal destruction. Severe neurological symptoms occur as a consequence of this phenomenon which is called primary demyelination. The sequence of events leading to primary demyelination during the course of viral infections of the CNS is only partially understood. Although it is well established that cytolytic infection of the Oligodendroglia cell can cause primary demyelination, mononuclear infiltrates in subacute and chronic courses of the disease indicate that immunological events may take part in this process (reviewed by Johnson (1)). For several reasons, investigations into the dynamic interactions between virus infection of the CNS and the local immune response cannot be conducted in man. (1) Usually clinical specimens are restricted to cerebrospinal fluid which gives limited information about pathological events occuring in the brain parenchyma (2). It is not known at which time point of the preceeding systemic infection, the virus enters the brain and biopsies are taken too rarely and infrequently to understand the kinetics of the events (3). The general absence of genetic homogeneity in man complicates attempts to detect the influence of the immunogenetic background on the course of the disease. In contrast, intracerebral infections of rodents with the murine hepatitis virus JHM (MHV-4) are excellent models to study the relationships between virus-induced demyelination and the local immune response. Based on the work of Cheever (2), animal models of JHM virus-induced demyelinating encephalomyelitis have been developed in mice as well as in rats (3–5). In recent years striking similarities in the course of the infection in both rodents have been detected which might give the impression that these two models can substitute for each other. However, subtle but important differences do exist. Therefore, in the present review attempts are made to summarize and compare the knowledge about demyelinating encephalomyelitides in rats and mice, giving emphasis to the role of the local immune response in the brain.

For coronaviruses, the glycoproteins have both historical and biological significance (1,2). Because some coronaviruses were difficult to isolate and propagate, their characteristic large, petal-shaped spikes first allowed coronaviruses to be identified as related agents in a common family. Viral glycoproteins play important roles throughout the life cycle of coronaviruses. Viral glycoproteins interact with receptors on the host cell membrane and are required for penetration of the viral genome into cells by fusion of the viral envelope with the plasma membrane or endosomal membranes. In virus-infected cells, Coronavirus glycoproteins may be glycosylated, acylated, oligomerized, cleaved into subunits by proteases, and transported to specific membrane compartments. The viral glycoproteins participate in assembly of virions, and the intracellular location of viral glycoproteins may determine the location of Coronavirus budding. Viral glycoproteins on the surface of infected cells may permit fusion with adjacent cells, and may make the cell susceptible to immune cytolysis or cell-mediated cytotoxicity, or permit hemadsorption. Epitopes of viral glycoproteins may be recognized by neutralizing, non-neutralizing or hemagglutination-inhibiting antibodies. Thus, elucidation of the structure and functions of Coronavirus glycoproteins is of central importance in understanding the replicative cycle and pathogenesis of coronaviruses.

In 1962 Caspar and Klug conjectured that self-assembly of equivalent or quasi-equivalent protein subunits and viral nucleic acid produces either icosahedral or helical structures according to the biological functions required (1). Some 15 years later Wengler introduced the terms “transcription helices” and “translation helices” to describe the relationship between helical ribonucleoprotein (RNP) structure and genome function for animal viruses containing single-stranded RNA (2). In transcription helices the RNA genome is transcribed into complementary nucleic acid, without permanent disassembly of the RNP. In translation helices the RNA is liberated from the RNP and translated into protein. To account for the fact that no examples of enveloped viruses containing translation helices had been described, Wengler speculated that “the forces exerted on the viral RNP during budding necessitate the design of a helical RNP of such high stability that RNA cannot be released for translation in vivo. Therefore, translation helices will not be present in viruses which obtain a viral membrane by budding”.

In 1984, the appearance of a new porcine Coronavirus related to TGEV was suspected based on an unexpected but widespread prevalence of antibodies to TGEV found in the swine population of several European countries. Most remarkable was the observation that this widespread occurrence of TGEV antibodies was seen in the absence of previous outbreaks or epizootics of diarrhea and also the fact that such findings were made in countries, e.g. Denmark, which had never experienced TGEV infection previously. The ease with which the virus spread, not only within a country, but also across national borders, pointed towards long distance virus transmission, almost certainly by the aerogenic route.

During the last decade recombinant DNA technology has been successfully applied to the development of ‘new’ vaccines. Although there are many examples of successful vaccines which have been developed using the ‘classical approach’ e.g. inactivated, attenuated and subunit vaccines, the demand for a new generation of vaccines is evident. The risk of the escape of a pathogen from a vaccine production facility, the difficulties associated with the production of viral subunits, the high mutation frequency observed in many RNA viruses and the possibility of genetic reassortment and recombination have stimulated researchers to explore new avenues of vaccine biotechnology.

The prediction of boundary layer transition was initially approached by asking where the laminar boundary layer first becomes unstable to what were then thought of as temporally growing instability waves (commonly referred to as Tollmien-Schlichting waves for inviscidly stable flows). However, it eventually became clear that the transition point (or better, the transition Reynolds number) is strongly affected by the specific details of the free-stream disturbance environment, and some of the research got redirected toward understanding just how it was that instability waves got generated by that environment, which was subsequently termed the receptivity phenomenon by Morkovin (1969). It was natural for experimentalist to study this phenomenon by imposing controlled, small amplitude, harmonic disturbances (i.e., disturbances of a single frequency, say ω) on thier flows, which then generated a spatially growing shear wave of the type referred to simply as an amplifying wave by plasma physicists who, incidentally, recognized very early on that these spatially growing waves are intimately connected to temporally growing instabilities.

The genomic RNA of coronaviruses has two unique features. Firstly, it is one of the largest stable RNAs known to exist in nature and is unquestionably the largest viral genomic RNA. The complete sequence of avian infectious bronchitis virus (IBV) RNA shows that its size is 27.6 kilobases (kb) (Boursnell et al., 1987). Although the complete sequences of other Coronavirus genomic RNAs are not yet available, preliminary data from several laboratories indicate that the genomic RNA of mouse hepatitis virus (MHV) is as long as 32 kb (Shieh and Lai, unpublished observations). The large size of these RNAs poses a theoretical quandary for the replication of Coronavirus RNA, considering the high error frequency of RNA-dependent RNA synthesis observed in some systems (Holland et al., 1982; Steinhauer and Holland, 1986). How does Coronavirus RNA replicate faithfully despite the high error frequency of RNA synthesis? It is possible that a proof-reading mechanism operates to correct unavoidable mistakes which are expect d to occur in almost every RNA molecule of this size. Secondly, Coronavirus RNA contains a leader sequence (approximately 72 nucleotides) which is repeated at the 5′-end of every subgenomic mRNA species. This structural organization appears to be similar to that of most of eukaryotic mRNAs which contain leader sequences derived by RNA splicing. Yet the Coronavirus RNA genome does not have consensus splicing signals and the virus replicates exclusively in the cytoplasm (Wilhelmson et al., 1981; Brayton et al., 1981), where there is no conventional RNA splicing machinery. Furthermore, UV transcriptional mapping studies suggest that Coronavirus mRNA species are transcribed independently (Jacobs et al., 1981), instead of being derived by cleavage of a precursor RNA. Thus, a new transcriptional mechanism must operate to transcribe Coronavirus mRNAs.

Pulp and paper mill effluents are complex mixtures of dissolved lignin and cellulose degradation products and other substances extracted during the pulping process. The toxicity of these effluents to fish has been documented (Howard and Walden, 1971; Wande, 1976; Walden and Howard, 1977). A number of investigators have shown that effluents and process streams from pulp and paper mills are mutagenic in Salmonella (Ander et al., 1977; Eriksson et al., 1979; Douglas et al., 1980) and cause chromosome damage in mammalian cells (Douglas et al., 1980). Over 300 compounds have been identified in studies on various pulp and paper mill effluents (reviewed in CPAR, 1978). Because of the extensive use of chlorine in the bleaching process, many of these compounds contain chlorine substitutions. Since first chlorination-stage liquors are consistently among the most mutagenic by-products of the pulping process, it has been suggested that chlorinated substances are responsible for a major portion of the mutagenicity found (Bjorseth et al., 1979; Nestmann et al., 1979; Nestmann et al., 1980; McKague et al., 1981; Rapson et al., 1980).

The rapid growth and development of diagnostic ultrasound is best evident in the significant technical advances apparent in instrumentation and its resultant increased capabilities. Unfortunately parallel advances in camera systems and photographic systems have not as yet been as apparent. At the present time, Polaroid film is most widely used in diagnostic ultrasound because of its easy access and convenience. The rapid growth of ultrasonic units utilizing photographic film for permanent recording of images necessitates a reassessment of available films and photographic papers for this purpose. In an attempt to establish the most desirable film and photographic paper for ultrasonic purposes, evaluation of currently available photographic materials were reviewed. Before such a review is presented a brief summary of some basic photographic and ultrasonic principles is necessary.

Various types of simple separation on paper have been described as fore-runners of paper chromatography, among them a method of Runge in 1850, and the process called ‘capillary analysis’ (Goppelsroder, 1909). Such methods were really more like adsorption chromatography, and paper chromatography as it is now understood was a development of the partition system introduced by Martin and Synge in 1941 (see Chapter 2). One of the solids which can be used to support the stationary phase is cellulose powder (p. 38). Consden, Gordon and Martin[l] in 1944 separated the amino-acids and peptides in wool protein hydrolysates by a method in which the powder column was replaced by a sheet or strip of paper, freely suspended in a vapour-tight vessel.

IJP is among one of several non-impact printing technologies which has recently established a very definite niche in the competitive and burgeoning computer printer market. The basic principle of UP is to force an inviscid ink through a small nozzle or array of nozzles onto paper and form an image by means of computer control. Basically there are two modes of generating ink drops, viz., continuous and impulse. In view of the current and projected range of print speeds, drop sizes, print resolution and impact velocities, continuous and impulse UP demands some rather unique paper properties to fulfill print quality requirements.

Radioactive tracer techniques, coupled with chemical analysis by paper chromatography, became important in biochemical research in the late 1940’s, and today many investigations into intermediary and other aspects of metabolism rely on these methods. Soon after the marriage of chromatography to the use of tracers, various instruments were constructed which were able simultaneously to locate the positions of radioactive compounds on paper chromatograms and to determine the amount of radioactivity in each separated compound. Such devices are now available commercially in many different designs, and are intended for the scanning and counting of one-dimensional chromatograms only.

Assay of C14-labeled compounds isolated from metabolic experiments has been greatly aided by the high counting efficiency of liquid scintillation spectrometers and the ease of preparing samples for such assay. Difficulties arise, however, in liquid scintillation assay of (A) compounds isolated on paper chromatograms and (B) protein, because it is not easily soluble in most scintillation mixtures. The present report deals with improved methods for liquid scintillation assay of C14-compounds isolated by paper chromatography and of C14-labeled protein.

It is now common to analyze a concentration profile obtained by electrophoresis or gas chromatography using Gaussian distribution properties. The theory of chromatography [1] suggested that a similar type of analysis might also be valid for paper chromatography. The present study indicated the validity of this analytical method in the particular case of paper chromatography, provided that certain precautions are taken [2]. We propose here to point out its essential features.

Mass screening for congenital hypothyroidism in newborns has been developed because the irreversible mental retardation caused by this disorder can be prevented by early treatment. These programs include measurement of thyrotropin or total thyroxine (T4), or both, in dried blood samples. Measurement of total T4 is useful for detecting primary, secondary, and tertiary hypothyroidism, but gives false-positive results for subjects with abnormal concentrations of thyroxine-binding globulin (TBG), who do not need to be treated. Hence, we developed an enzyme immunoassay (EIA) and a radioimmunoassay (RIA) for measuring free T4 (FT4) in dried blood samples on filter paper.

The research of the past several years has produced a substantial body of knowledge concerning the design of parallel algorithms and their implementation on various architectures. In many ways the enterprise has been highly succesful: a number of fundamental principles of parallel algorithm design and parallel communication have emerged, and the foundations of a rich mathematical theory have been laid. Despite these successes, the theoretical work has had relatively little influence on developments in parallel computer architecture, or on the application of parallel computation techniques to fields such as computer vision, artificial intelligence, combinatorial optimization and scientific computing. We must continue to work on the development of models of parallel computation that are sufficiently abstract to support a theoretical investigation, and yet reflect the objectives, constraints and design considerations that arise in practice.

Determining the type and amount of organophosphate pesticide residue in food products is a complex problem, and one which concerns both the companies which manufacture the pesticides and the Governmental agencies which enforce their proper use.

An early example of the working relationship between the electrical transmission of images and silver halide photography or phototelegraphy was the Kopiertelegraph (from the German Kopagraphegrafen for copying telegraphy), the invention of engineer Gustav Grzanna, born in Breslau. In 1901 Grzanna presented his fernschreiber (teleprinter) that used a scanning stylet at the transmitter to send an electrical signal via telegraph lines. At the receiver the image was written by a mirror galvanometer, a small mirror on a magnet held within the field produced by two electromagnetics, one for X and the other for Y translation. Light projected onto the mirror was reflected to scan and expose photographic paper (Huurdeman 2003). The Grzanna Kopiertelegraph Company of Dresden went out of business in 1905, unable to compete with the Telautograph of German physicist Arthur Korn that was introduced in 1902, as noted in Chap. 75 (Suplee et al. 1906, p. 1105). Korn’s rotating scanning drum was a precursor of the photographic facsimile machines used by organizations like newspapers and police departments for many years.

DNA methylation serves to mark DNA as either a directed epigenetic signaling modification or in response to DNA lesions. Methods for detecting DNA methylation have become increasingly more specific and sensitive over time. Conventional methods for detecting DNA methylation, ranging from paper chromatography to differential restriction enzyme digestion preference to dot blots, have more recently been supplemented by ultrahigh performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) to accurately quantify specific DNA methylation. Methylated DNA can also be sequenced by either methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) or single-molecule real-time sequencing (SMRTseq) for identifying genomic locations of DNA methylation. Here we describe a protocol for the detection and quantification of epigenetic signaling DNA methylation modifications including, N6-methyladenine (6mA), N4-methylcytosine (4mC) and C5-methylcytosine (5mC) in genomic DNA by triple quadrupole liquid chromatography coupled with tandem mass spectrometry (QQQ-LC-MS/MS). The high sensitivity of the UHPLC-MS/MS methodology and the use of calibration standards of pure nucleosides allow for the accurate quantification of DNA methylation.

The concept of the Josephson energy emerges directly from the original predictions of Brian Josephson. Although it can be used to explain the behaviour of Josephson devices, the Josephson energy has no present applications. In this paper, we show that in the context of magnetic Josephson junctions, the Josephson energy offers a potential mechanism for controlling magnetic memory devices.

Dr. Flomenhaft’s paper began with vivid illustrations that made the point: Contrast in group and cultural approaches to health care holds not only for persons of dissimilar cultures but within each culture. I will use my experience in Taiwan to relate to the paper. In Taiwan, it was very evident to us that the nurses and nursing faculty were not aware of some of the most common sentiments and practices of persons in their own culture. Perhaps this represents subcultural differences, because the nurses were well educated, while many patients and families were not. Some things that these nurses were not fully aware about the patients included: (1) extensive use of fortune tellers (2) expensive financial expense for religious practices such as paying for vows and seeking services of ritual specialists (3) the extent to which grandparents influenced family decisions, sometimes disastrously. For example, the grandfather who refused to have a child operated upon until too late, and only then did so when a fortune teller indicated to his satisfaction that “out of evil good will come.” (4) the extent to which the nurses were unaware of how much pain the children suffered because the parents did not volunteer information.

This paper presents a schema that attempts to embrace all graphic language. The essence of the schema is shown in a matrix which presents a number of theoretical possibilities in terms of approaches to graphic language. One axis of the matrix describes the methods of configuration of graphic language, using such terms as pure linear, linear interrupted, list, linear branching, matrix, non-linear directed, non-linear open. The other axis describes the modes of symbolization of graphic language, using four somewhat crude categories: verbal/numerical, pictorial and verbal/numerical, pictorial, schematic. Numerous, examples are shown to clarify terms and the underlying concepts they describe. It is emphasized that the matrix is a device for directing thinking, rather than a means of defining graphic language. The paper is written from the standpoint of a practising graphic designer. The matrix is used to illustrate the wide range of approaches open to us in graphic language and the effect this is assumed to have on reading/viewing strategies and cognitive processes. It is mggested that the matrix is useful in focusing attention on two fundamental questions that ought always to be asked when deciding how a graphic message should be communicated: What should be the mode of symbolization and what should be the method of configuration? Legibility and related research is briefly reviewed in order to establish what light it throws on these questions; with a few notable exceptions it is found wanting. It is suggested that there is a need for more research that crosses the boundaries of the cells of the matrix. This paper is not the culmination of a sustained programme of research and brings no firm evidence to bear on any aspect of graphic language. It is the contribution of a graphic designer who has had the opportunity of associating with research workers concerned with the evaluation of graphic language, and is written as a tutorial paper to stimulate thought and discussion. It is an attempt to define the scope of graphic language and to show relationships between different approaches to it that have been, and can be, used. Throughout the paper, the totality of graphic language and its specifically graphic variables are emphasized. Though the approach may appear to be somewhat theoretical, it is intended that it should have practical implications.

A Strain of cellulose-decomposing bacterium 372–24D together with a saprophytic bacterium 372–24M were isolated from soil. On the basis of morphology, physiological properties and cellulolytic activity of these isolates, strain 372–24M was identified as Cellulomonas flavigena and strain 372–24M as Pseudomonas putida. They grew syntrophically in a liquid medium containing basal salts with paper pulp (73.3% cellulose) as sole carbon source. The cellulose was decomposed to the extent of 98% after 5-day culture. The cell protein yield was about 0,17 Kg per Kg of paper pulp used. The cell protein was rich in lysine, arginine, leucine and valine. After adjusting the pH of the culture broth to 10 and temperature to 60°C, one half of the cell RNAs could be degraded to mononucleotides by cell RNAase within 20 min. The products were isolated from the culture broth, purified and crystallized. They were identified at 5’-AMP, 5’-GMP, 5′-CMP and 5′-UMP. A complex process for the production of SCP and mononucleotides was developed.

The first paper was presented by Sir Geoffrey Vickers at the opening session of the meeting and is entitled “The Poverty of Problem-Solving”. His principal point is that systems analysis is not a technique for solving problems but rather an approach to understanding situations; that understanding may or may not be followed by some action involving a detailed second round of analysis. Systems analysis is viewed as offering a conceptual framework that helps make sense of what one knows already. The theme proposed by Vickers emerged frequently during the discussions throughout the week of the Advanced Research Institute. It is also a theme which emerges in many of the papers and thus Vickers’ paper has been included as part of the introduction to give some perspective to the arguments which follow.

Dr. Moskovic compared in his paper 30 patients treated with Amoxapine and Amitryptaline in order to compare their effectiveness in reversing depressive symptoms. Amoxapine had superior results and also showed less side effects for sedation, memory loss, akin-thesia, dry mouth, blurred vision, and light headedness. Suicidal reaction and impaired sleep were the symptoms that improved most rapidly. Hispanic patients were noted to require lower dosages, which is a common denominator of all papers and will be discussed in more detail later. Dr. Moskovic notes that Norepinephrine reuptake is blocked by Amoxapine, but not by Amitriptyline which may explain the differences in rapidity of onset of action.

In this study paper is modelled as a homogeneous structure where the cell wall layer of the fiber constitutes the main building unit. By this approach the macroscopic properties of paper are related to the properties of the constituent polymers cellulose and hemicelluloses. The effects of fiber orientation and the influence of moisture content on the elastic moduli and hygroexpansivity of paper is examined and compared to experimental data. It is advocated that the mechanical properties of paper are dependent on a mixture of transverse and longitudinal cell wall layer properties and not only on the proportion of fibers in any direction.

The sizing treatment of printing papers to make them resistant to penetration by liquids, for example, water or printing inks, also weakens the bond strength between the polymer and the paper in printing processes in which solid polymers create the image on plain, bond-type papers. The adhesion characteristics of a series of business papers treated with either rosin sizes or synthetic, cellulose-reactive sizing agents are described. It is demonstrated that the decrease in bond strength correlates with a decrease in paper wettability, as measured by capillary penetration of organic liquids of suitable surface tension, or as defined by surface energetics using the elution-gas-chromatography technique. Examples are presented, which show that these analytical techniques are effective in specifying paper performance in nonimpact printing technologies (for example, electrophotographic printing and resistive-ribbon, thermal-transfer imaging).

This paper is an introduction to three further technical papers on advanced teleoperation. We first give a brief history of this research project, recording the part played by Jean Vertut. We present the basic concepts of advanced teleoperation, starting with the necessity for coexistence of autonomy and transparency, emphasizing the virtual level in relation to the real level. In the following section we introduce the technical papers, the first of which is devoted to generalized master slave control and supervisory systems, the second to generalized information feedback, and the third to a description of an integrated experimental test bed. The paper ends with some thoughts on the future of advanced teleoperation.

As the consequences of climate change become apparent, metabolic engineers and synthetic biologists are exploring sustainable sources for transportation fuels. The design and engineering of microorganisms to produce bio-gasoline and other biofuels from renewable feedstocks can significantly reduce dependence on fossil fuels as well as lower the emissions of greenhouse gases. A significant amount of research over the past two decades has led to the development of microbial strains for the production of advanced fuel compounds. Crucial to these efforts are robust methods to quantify the amount of the biofuel compound being produced as well as the other metabolites that might be present during fermentation. Here, we provide a protocol for the quantification of branched-chain alcohols, specifically isobutanol and isopropanol, using high-performance liquid chromatography (HPLC).

Bioreactors are manufactured apparatuses that allow the generation of a specific environment for the highly controlled cultivation of living cells. Originally used for microbial production systems, they have found widespread applications in fields as diverse as vaccine production, plant cell cultivation, and the growth of human brain organoids and exist in equally diverse designs (Chu and Robinson, Curr Opin Biotechnol 12(2):180-187, 2001; Qian et al., Nat Protoc 13:565-580, 2018). Manufacturing of biologics is currently mostly performed using a stirred tank bioreactor and CHO host cells and represents the most "classical" bioreactor production process. In this chapter, we will therefore use the cultivation of suspension Chinese hamster ovary (CHO) cells for recombinant protein production in a stirred tank bioreactor as an example. However, general guidelines provided in this chapter are transferable to different bioreactor types and host cells (Li et al., MAbs 2(5):466-479, 2010).The preparation and operation of a bioreactor (also referred to as upstream process in a biotechnological/industrial setting) is comprised of three main steps: expansion (generation of biomass), production (batch, fed-batch, or continuous process), and harvest. The expansion of cells can last from few days to weeks depending on the number of cells at the start, the cellular doubling time, and the required biomass to inoculate the production bioreactor. The production phase lasts a few weeks and is a highly sensitive phase as the concentration of different chemicals and physical parameters need to be tightly controlled. Finally, the harvest will allow the separation of the product of interest from large particles and then the desired material (cell culture supernatant or cells) is transferred to the downstream process.The raw materials used during the upstream phase (all three steps) need to be aligned with the final purpose of the manufactured product, as the presence of residual impurities may have an impact on suitability of the final product for a desired purpose.

There are three essential steps involved in bioethanol production from lignocellulosic biomass feedstocks. They are pretreatment, hydrolysis, and fermentation process. Among them, biomass pretreatment is an expensive and energy-intensive process used to remove the lignin and make the feedstock amenable for bioethanol production. The hydrodynamic cavitation can also be used for biomass pretreatment process. In order to improve the effectiveness of biomass pretreatment, a combination of any two methods of physical, chemical, and biological pretreatment can be used. A combination of the hydrodynamic cavitation pretreatment of biomass with the chemical or biochemical catalyst can be performed better than the individual pretreatment method. In this chapter, a protocol is describes the biomass pretreatment via a combined hydrodynamic cavitation with biocatalyst process.

Worldwide demand for ethanol alternative fuel has been emerging day by day owing to the rapid population growth and industrialization. Culturing microalgae as an alternative feedstock is anticipated to be a potentially significant approach for sustainable bioethanol biofuel production. Microalgae are abundant in nature, which grow at faster rates with a capability of storing high lipid and starch/cellulose contents inside their cells. This process offers several environmental advantages, including the effective utilization of land, good CO2 sequestration without entering into "food against fuel" dispute. This chapter focuses on the methods and processes used for the production of bioethanol biofuels from algae. Thus, it also covers significant achievements in the research and developments on algae bioethanol production, mainly including pretreatment, hydrolysis, and fermentation of algae biomass. The processes of producing biodiesel, biogas, and hydrogen have also been discussed.

Biofuels offer a solution to combat climate change and secure energy surplus. Among the various sources for biodiesel production, the seed of oilseed crops is primary raw material. The biodiesel industry demands a supply of good quality oil so that it can reduce processing costs and price of biodiesel. In general, the oils with low free fatty acid contents are considered as good quality oil and for which the quality of the oil should be analyzed in seed lot for biodiesel production. Currently, oil quality testing is done to the oil extracted from seed lot using sophisticated instruments. However, the analysis of oil seed lot is not tested, which forms the basic materials for oil extraction. Therefore, analysis of the quality of raw materials (seed lot in this case) is mandatory for assessing oil quality.Till now, there is no standard method available for screening the quality of the oilseed before biodiesel production. The free fatty acid (FFA) content of the oil is the critical factor for biodiesel production. In seeds, the FFA content of oil is directly associated with seed viability. In this chapter, an easy-to-perform protocol is presented for determining the seed viability potential, which is having a significant positive association with FFA content of the seed.

Yarrowia lipolytica produces a range of valuable biotechnological products from natural metabolites and enzymes to heterologous proteins. The production of these products is affected by medium composition and various environmental factors. Here we describe bioprocess development for a recombinant laccase production by Y. lipolytica. At first, response surface methodology (RSM), as a statistical technique for design of experiment (DOE), is used for the optimization of medium composition in flask level. Then, results of RSM are applied to increase laccase production in controlled conditions of the bioreactor.

Rare earth metals, in the range of 0 to 250 micrograms, have been extracted quantitatively from perchloric, nitric or hydrochloric acid solutions by strong acid ion exchange paper disks in the sodium ion form. After the exchange is completed, the ion exchange paper disk is placed in a rotating sample holder and the amount of rare earth metals exchanged is determined by x-ray emission spectrography. At the 10 microgram level, the accuracy has a mean error of 2% with a precision of 1.5% relative standard deviation. The procedure has been applied to Sc+3, Y+3, Ce+4, Pr+3, Nd+3, Sm+3, Eu+3, Gd+3, Tb+3, Dy+3, Ho+3, Er+3, Tm+3, Yb+3 and Lu+3.

If one is faced with the problem of determining the distribution of radioactivity in a paper chromatogram, there are several assay techniques available. The chromatogram may be scanned in a strip counter and the radioactivity estimated by measuring areas under each peak or by use of an electronic integrator [1]. The paper strip can also be cut into appropriate sections and the radioactivity of each section determined under a Geiger counter. Depending on the thickness of the paper, the counting efficiency of these techniques is in the range of 3–10%. More serious than the inefficiency is the variation in efficiency, which makes quantitation difficult.

In most cases the production technology has to be carefully considered for the overall robot design. A practical approach for setting up performance specifications with the help of worksite analysis will be presented with an overview of the most important design philosophies. The paper closes with important results achieved from worksite analysis.

John Bowlby began his chapter (with acknowledgments to Robert Hinde) with a statement of six ways in which studies of animal behavior can contribute to a study of human behavior. Two of these pertain especially to experimental studies, two perhaps specifically to naturalistic studies, and two to studies of both types. Let me first consider experimental studies and their contributions with particular reference to Dr. Suomi’s chapter, and then turn to naturalistic studies, referring both to Dr. Bowlby’s paper and to some work of my own.

The evaluation of energy resources is a vital component in the determination of energy strategy on which the formulation of energy policy is based. It is however an uncertain art since the existence of only a portion of mineral reserves can be considered as a fact, the remainder being at best speculative. W. C. Stitt’s paper addresses problems in the state of the art of modeling of crude oil and natural gas resources in the USA giving examples of the type of problems encountered. His physical description of the resource base utilizes the McKelvey diagram in which the physical characteristics of the deposits are distilled into two attributes, one of quantity by the degree of certainty and the other by cost of extraction. The values of these attributes are the input information required for the potential supply functions used in energy policy analysis. The known reserves usually represent only enough of the resource to underpin commercial operations to the appropriate planning horizon of the industry; information for periods beyond this can only be inferred from current exploration data which can be highly variable inquality.