Historical perspectives

Historically, X-ray crystallography was the only method for determining three-dimensional structures of macromolecules at atomic resolution. The rise of NMR as a rival technique resulted from a combination of NMR techniques on the experimental side and corresponding algorithmic developments on the theoretical side.1 

Even before the common use of Fourier transform NMR, it was known that the homonuclear nuclear Overhauser enhancement (NOE) could be used to identify pairs of protons separated by a few angstroms in space.2 It was also clear, however, that many such distances and accurate assignments to specific protons would be needed to define a solution structure fully. The advent of two-dimensional NMR was a major step toward providing the necessary data,3-4 but the introduction of the two-dimensional NOE measurement (NOESY)5-6 truly revolutionized the ability both to assign spectral peaks and to acquire large quantities of distance information. 

FIGURE 17.5 Water flow in the Everglades under (a) historical conditions, (b) current conditions, and (c) conditions envisioned upon completion of the restoration. (From U.S. Army Corps of Engineers, Jacksonville District, Florida.) 

Materials are probably more deep seated in our culture than most of us realize. Transportation, housing, clothing, communication, recreation, and food production— virtually every segment of our everyday hves is influenced to one degree or another by materials. Historically, the development and advancement of societies have been intimately tied to the members abOity to produce and manipulate materials to fill their needs. In fact, early civilizations have been designated by the level of their materials development (Stone Age, Bronze Age, Iron Age).  

The development of many technologies that make our existence so comfortable has been intimately associated with the accessibility of suitable materials. An advancement in the understanding of a material type is often the forerunner to the stepwise progression of a technology. For example, automobiles would not have been possible without the availability of inexpensive steel or some other comparable substitute. In the contemporary era, sophisticated electronic devices rely on components that are made from what are called semiconducting materials. 

Understanding of the issues involved in superposition errors has evolved slowly. Consequently, the reader is liable to encounter a number of different attitudes and means of handling the problem over the years in the literature. This section is intended to provide some perspective on the problem so that the reader will be able to critically assess the impact that superposition error might have on a given set of calculations in the literature. 

Although many researchers ackowledged that there was some inconsistency in using a larger basis set for the complex than for the monomers, there was initial reluctance to accept the counterpoise procedure as a valid means to correct the problem when it was first introduced. The chief source for this skepticism lay in the numerical results. Many of the early calculations of H-bonded complexes relied on fairly small and inflexible basis sets. It is now known that bases of this type tend toward potentials that are much less attractive than the true potential. Limitations of the era also prohibited application of correlation in most cases, eliminating a major attractive component. As a result, the H-bond attractions corresponding to these treatments are much too weak. It was only the superposition errors that were hidden in the calculations that permitted the final results to be even slightly attractive. In other words, if one does not analyze the results carefully, one can easily be misled since the spurious attractive nature of the BSSE can compensate in some sense for the unsatisfactory character of the calculations themselves. 

For example, an STO-3G calculation of the water dimer, if left uncorrected for basis set superposition, can yield an interaction energy not very different from experimental expectations. But when the superposition error is removed, the remaining potential, the true HF/STO-3G potential is not attractive at all, but indicates the water molecules would repel one another and not form a H-bonded complex. Rather than recognize this observation as a legitimate failing as an error due to the STO-3G basis set or to the absence of correla- 

But such an approach is shortsighted. One must understand that precise reproduction of an experimental result is coincidental at best when using a crude method with known weaknesses. After all, a minimal basis set without correlation does not offer a realistic version of a molecular system, so why should one take an experimental H-bond energy as a criterion as to whether counterpoise is an appropriate correction By removing the BSSE, one approaches the true picture of a given theoretical model, in this case the HF/STO-3G version of the water dimer. Even with larger and more flexible basis sets, one should not necessarily expect the calculations to duplicate experiment. Such an expectation might lead one to erroneously conclude that counterpoise corrections do not improve the accuracy of the calculations .  

Nonetheless, the early disagreement of counterpoise corrected H-bond potentials with experiment spawned a number of variants of the technique which reduced the BSSE correction and left the potential more attractive than if the full error were removed. Some of these methods justified themselves on the grounds that the electrons of one molecule should not expand into the orbital space of the partner molecule that is already occupied by elec-trons . Hence, damping factors were introduced or more formal means of permitting the electrons of molecule A to partially occupy only the vacant MOs of molecule B, and vice versa - Another technique proposed employing a perturbing charge field gen- 

Many interviewees referenee Tunisia s first president, Habib Bourguiba, in their responses. One of Bourguiba s main priorities for the nascent country was education, and this emphasis on education as a key to Tunisia s future has continued through the subsequent administration and into the new leadership estabhshed in 2011. The historical reference to education as an elemental priority seems to ground perspectives on Tunisian EE in a deep and valued history. 

In the faculty of an engineering institution, respondents report that efforts are made to occasionally bring industry into the classroom to teach a module or a class. This is an efficient and effective way of incorporating industry professionals and irmovative perspectives into the schools. However, it is reportedly difficult to find 

Technopoles, or technoparks that physically jrrxtapose small and medium enterprises (SMEs) and rrrriversily camptrses, were set up just before the new millenrtium to constitute the nerve centers of a rrational network of scientific and technical research... (RepubUc of Ttrrrisia, MESRST 1999). Respondents see these Trrrrisian 

Tunisia s main professional organization for engineers is the Conseil de I Ordre des Inginieurs. This group is a loose affiliation, in which membership is often re- 

MESRST, there are some that have a double tutelle because of their subject focus. For example, the telecommunication school for technicians in Tunis, also known as ISET COMM, also falls under the tutelle of the Ministry of Technology. This allows the schools a bit more freedom than their single tutelle peers, which respondents perceive as valuable for students and perhaps desirable for industry and opportunities to get hands-on practice. 

it takes some time. What does this cost in terms of productivity, utilities or work force The only way to be sure the petroleum product stays on specification is to make the 

Of what is the Universe made This question has been the subject of serious scientific study for more than a century. One of the first papers on the subject, entitled The relative 

Their table included isotopic abundances as well as elemental abundances. Since the Suess and Urey table was published, subsequent work has primarily refined the determinations of the cosmic abundances through improved measurements of meteorites, a better understanding of which meteorites should be considered for this work, improved measurements of the solar composition, and a better understanding of nuclear physics. 

In recent decades, spectroscopy has revealed that the elemental and isotopic abundances in the galaxy vary with radial position and that the Sun has a somewhat different composition than the molecular clouds and diffuse interstellar medium in the solar neighborhood. For this reason, we can no longer think of the solar system abundances as truly cosmic abundances. 

Synthetic analog clusters have played a pivotal role in development of Fe-S cluster biochemistry. Indeed, the synthesis and characterization of clusters with [Fe2( t2-S)2], [Fe4( (,3-S)4], and linear [Fe3( t2-S)4l cores by Holm and co-workers (47, 48) were crucial in establishing the properties of these clusters and identifying these types of centers in biological systems. However, the synthesis of a cluster with the physi- 

As dramatic as the developments in the area of SPE media have been over the last 40 years, the development of instrument technology has even made greater 

In the early 1970s, the introduction of the quadrupole mass spectrometer changed the landscape of residue analysis in the coming decades dramatically. The combination of GLC with the mass spectrometer as a detector proved to become the major tool for residue analysis for the next 20 years. 

Model HP 5890 was specifically designed for residue analysis and gained widespread acceptance as a standard instrument for GC/MS residue applications. 

Several other interface designs were introduced over this period, including continuous flow fast atom bombardment (CFFAB) and the particle beam interface (PBI), but it was not until the introduction of the API source that LC/MS applications really came to the forefront for quantitative analysis. Early work by Muck and Henion proved the utility of an atmospheric pressure interface using a tandem quadrupole mass spectrometer. 

Observations from various systems, including yeast, suggest that phosphorylation and dephosphorylation of proteins play important roles in the mitotic and meiotic cell cycles and the differentiation of germ cells. Extracts from mitotic HeLa cells contained phosphoproteins also present in other mitotic and meiotic cell types, but not in interphase cells (Davis et al., 1983). Exposure of Xenopus oocytes to progesterone results in a burst of protein phosphorylation shortly before GVBD (Mailer et al., 

The early sixties saw a broad and intense interest in the making of the heretofore unknown molecular compounds with a boron-metal bond (8). In 1963, the first compounds with boron-metal r-bonds, 

In 1970, the synthesis of the orange-red sandwich cation 1 from cobaltocene and PhBCl2 (1) marked a further starting point in the chemistry of boron metal compounds. The presence of a planar benzenoid C5H5B ligand moiety in 1 was deduced from XH and UB NMR data (1). This was made ironclad by two X-ray structure determinations which revealed typical centrosymmetric sandwich structures for the 19-e complexes Co(C5H5BOMe)2 (6) (21,22) and Co(C5H5BMe)2 (7) (22) as shown in Fig. 1. 

A second and independent entry into the field was provided by Ashe and Shu with their synthesis of lithium 1-phenylboratabenzene 8 in THF 

Borabenzene itself (2) has remained elusive. A qualitative contention that 2 should be a highly reactive species that can be stabilized by Lewis bases (7) has been reinstated by semiempirical and ab initio calculations (24,25). Moreover, the calculation predicts a singlet ground state (2a) and a singlet (2a)-triplet (2b) separation of approximately 1 eV (25). 

In mass spectra of borabenzene metal complexes, ions of type [M(C5H5B)]+ are commonly observed [Co(CsH5B)]+ decays via loss of an uncharged C5H5B fragment as evidenced by the observation of a metastable ion peak (7). 

Because of the large number of known ubiquitylation substrates and since E3s recognize specific proteins or modified forms of proteins, the number of E3 specificities is necessarily enormous. However, until recently few E3 had been molecu-larly characterized. By 1992, for example, 13 E2s had been described in yeast [6j. 

Of these, 11 function with ubiquitin and one with each of two different ubiquitin-like (UbL) proteins. Sumo and Nedd8/Rubl [2]. However, while several yeast and metazoan E3s had been identified biochemically by that time, the primary amino acid sequence was known only for a single E3 [7]. This was the Saccharomyces cer-evisiae Ubrlp, which had been studied extensively by Varshavsky and co-workers in delineation of the N-end rule [8, 9]. Its mammalian ortholog, E3a, was the prototypical E3 used in the description of the basics of the ubiquitin pathway by Hershko and Ciechanover [1, 10]. 

As HECT domain function was being elucidated, studies in the mid-1990s on cell-cycle regulation led to the initial description of SCF E3s. These were first characterized as containing Skpl, Cullin-1, and an F-box-containing protein [16, 17]. 

Also identified during the mid-1990s was the APC (anaphase promoting complex - also known as the cyclosome), another multi-subunit cullin-containing E3 that mediates ubiquitylation of mitotic cyclins [18, 19]. Mdm2, initially thought to be a HECT domain variant, was shown in 1997 to have E3 activity towards p53 in vitro [20]. For the non-HECT E3s no common structural feature had been detected. Thus, by 1997 the only defined molecular signature for E3 activity was the HECT domain. 

The term RING finger was first coined by Freemont and colleagues referring to a gene product in the MHG class I locus [22]. Their apparent exuberance led to the 

Although the formation of hippuric acid is a conjugation reaction, many metabolic conversions require the ability of living organisms to oxidize compounds and in 

Hit and Lead Profiling. Edited by Bernard Faller and Laszlo Urban Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32331-9 

As many of us who are involved in clinical trials will know, the randomised, controlled trial is a relatively new invention. As pointed out by Pocock (1983) and others, very few clinical trials of the kind we now regularly see were conducted prior to 1950. It took a number of high profile successes plus the failure of alternative methodologies to convince researchers of their value. 

One of the largest trials ever conducted took place in the US in 1954 and concerned the evaluation of the Salk Polio Vaccine. The trial has been reported extensively by Meier (1978) and is used by Pocock (1983) in his discussion of the historical development of clinical trials. 

Within the project there were essentially two trials and these clearly illustrated the effectiveness of the randomised controlled design. 

Statistical Thinking for Non-Statisticians in Drug Regulation Richard Kay 2007 John Wiley Sons, Ltd ISBN 978-0-470-31971-0 

A further 0.75 million children in other selected schools in grades one to three were to be included in this second trial. All parents were approached for their consent and those children where consent was given were randomised to receive eitherthe vaccine or a placebo injection. The trial was double-blind with parents, children and investigators unaware of who had received the vaccine and who had not. 

This new law, known as the Pure Foods and Drugs Act, prevented the importation of adulterated and spurious drugs and medicines, and required that all ingredients be identified on the drug label, thus ending the era of secret nostrums (6,7). 

This fluid extract is prepared from Cannabis saiiva grown in America. Extensive pharmacological and clinical tests have shown that its medicinal action cannot be distinguished from that of the fluid made from imported East Indian cannabis. Introduoed to the medical profession by us. 

Average dose. 1 1,2 mins. (0.1 cc). Narcotic, analgesic, sedative.  

From the Parke. Davis Company 1929-1930 physicians catalog 

Following the passage of the FD C Act, FDA was authorized to permit NDAs for new drugs, but the agency could not approve them affirmatively (see Section 505 of the FD C Act). One such NDA was for the botanical rauwolfia Rauwolfia serpentina), first marketed in the United States in 1953. Used in India for centuries, root of rauwolfia was sold in the United States as a treatment for hypertension. More than a dozen NDAs were subsequently recorded for the drug, all of which were discontinued by 1982, as better antihypertensives came to market (Table 1). 

Much of the research on fluorocarbons was pioneered by researchers at E. I. DuPont de Nemours Company. The technology quickly centered on derivatives of halocarbons. These gases, which were sold under the trademark Freoi , had the general formula C H FyCf, where x + y + z=2n +2. 

In 1938, while attempting to prepare fluorocarbon derivatives, Roy J. Plunkett, at DuPont s Jackson Laboratory, discovered that he had prepared a new polymeric material. The discovery was somewhat serendipitous as the TFE that had been produced and stored in cylinders had polymerized into poly(tetra-fluoroethylene) (PTFE), as shown in Eigure 4.2. It did not take long to discover that PTFE possessed properties that were unusual and unlike those of similar hydrocarbon polymers. These properties include (1) low surface tension, (2) high Tm, (3) chemical inertness, and (4) low coefficient of friction. All of these properties have been exploited in the fabrication of engineering materials, wliich explains the huge commercial success of PTFE. 

The perfluoroalkylethyl alcohol (Zonyl Ba ) has proven to be a very versatile synthetic intermediate. The ethyl group spacer in the alcohol separates the electronegative perfluoroalkyl group from the alcohol moiety, which leads to 

In 1935, the Committee was renamed the Analytical Methods Committee (AMC) but the main analytical work was carried out by sub-committees composed of analysts with specialised knowledge of the particular application area. The earliest topics selected for study were milk products, essential oils, soap and the determination of metals in food colourants. Later applications included the determination of fluorine, crude fibre, total solids in tomato products, trade effluents and trace elements, and vitamins in animal feeding stuffs. These later topics led to the publication of standard methods in a separate booklet. All standard and recommended methods were collated and published in a volume entitled Bibliography of Standard, Tentative and Recommended or Recognised Methods of Analysis in 1951. This bibliography was expanded to include full details of the method under the title Official, Standardised and Recommended Methods of Analysis in 1976 with a second edition in 1983 and a third edition in 1994. 

The work of the AMC has continued largely unchanged over the years with new sub-committees being formed as required and existing ones being disbanded as their work was completed. In 1995, the Council of the Analytical Division set in place a strategic review of the AMC in view of the changing need for approved analytical methods and the need to develop future direction for the AMC as it moves into the next millennium. 

The aim of the AMC was reaffirmed to be participation in national and international efforts to establish a comprehensive framework for the appropriate quality in chemical measurements, which is to be realised by achieving five objectives  

R02C(CH2)nZnI PhC02CH2ZnI PhC02(CH2)4ZnI ICH2ZnI 

As seen in Table 1.1, forming methods using fine powder feeds have been practised for centuries in the preparation of such products as tiles, bricks and tablets. Brief descriptions of modern forming methods used mainly in the pharmaceutical, powder metallurgy and ceramics fields are given in Table 1.2. Such forming methods are generally outside the scope of the present treatment. Information on these techniques is well documented elsewhere the reader is directed to the references noted in Table 1.2. 

Size enlargement to improve the bulk properties of particulates is the subject of this book. Techniques to accomplish this beneficiation may be classified according to the principal method used to bring particles together into agglomerates. The categories used here are  

Of course, in any classification system areas of overlap are unavoidable. Some size enlargement processes involve more than one agglomeration mechanism. For example, thermal after-treatment is quite common to harden 

Forming-type methods properties of individual compacts are controlled 

Vibratory compaction Vibration is applied to a mass of powder in a container-mold so that the particles seek a state of closest packing. Part subsequently strengthened, e.g. by sintering.  

Copyright 1990 by Academic Press, Inc. All rights of reproduction In any form reserved. 

As a part of his classic study of reactive free radicals in the early 1930s, Paneth observed that methyl radicals react with a heated antimony mirror to produce tetramethyldistibine (22) (27). This distibine has quite remarkable properties. It forms intensely colored red crystals which melt reversibly to a yellow oil. Similarly, solutions of tetramethyldistibine are pale yellow. Although these color changes are clearly due to changes in phase rather than strictly temperature, they have been termed thermochromic 

The dibismuthine occurred as violet crystals which melted to a red-yellow liquid prior to decomposition below room temperature. 

Nine other thermochromic distibines have been reported. All show a yellow melt, but the solid colors range from deep yellow to violet-blue. Seven thermochromic dibismuthines are known. The liquid colors are all red while solid colors are variable. The thermochromic distibines and dibismuthines are listed in Table II (7,10,17a,21,23-41) along with the melting points and colors of the crystals. Nonthermochromic dibismuthines are collected in Table III (20,29,32,42). 

Measurements of dielectric properties have been used to monitor chemical reactions in organic materials for more than fifty years. In 1934, Kienle and Race 11 reported the use of dielectric measurements to study polyesterification reactions. Remarkably, many of the major issues that are the subject of this review were identified in that early paper the fact that ionic conductivity often dominates the observed dielectric properties the equivalence between the conductivity measured with both DC and AC methods the correlation between viscosity and conductivity early in cure the fact that conductivity does not show an abrupt change at gelation the possible contribution of orientable dipoles and sample heterogeneities to measured dielectric properties and the importance of electrode polarization at low frequencies. 

Since 1958, an extensive experimental literature has developed, primarily on epoxies, and, to a lesser extent, on polyesters, polyimides, phenolics, and other resins. Work in this area has been greatly stimulated by the increasing importance of thermosets as matrix resins in fiber reinforced composites, and by significant improvements in instrumentation and measurement methods. 

There is a literature gap between 1922 and 1935 when the concept of the hydrogen bond appears to have been forgotten. This was the period when both theory and experiment were focusing on the strong interatomic interactions in chemistry as represented by the covalent, ionic, and metallic bonds. The Braggs and collaborators were determining the crystal structures of the simple inorganics to form the basis of a new science, Crystal Chemistry [11]. 

Tfcble 1.1. Some early formulations of hydrogen bonds 

Hydrogen nucleus between two octets constitutes a weak bond [8, 9] 

The illustrations from Astbury s 1933 paper shown in Fig. 1.1 imply some kind of bonding between NH and C=0 groups, but the term hydrogen bridge or bond is never used in his model of polypeptide folding. 

Surprisingly, it was not until 10 years later that Huggins published a series of definitive papers on hydrogen bonding in organic molecules [18], in ice and liquid water [19], and Bernal and Megaw in hydroxide minerals [20]. It appears to have been these three authors who supplied the first descriptors. Huggins used the term 

FIGURE 1.1 Red pottery vase with a contracted waist, a black design on a red base that covers the earthen ware (brown). It was excavated at Lan-chou, Kansu, in 1968, and is 18.3 cm in height, from the third millenium B.C. Taken from The Genius of China [2]. 

FIGURE 1.2 Yang-shao bowl excavated in 1954—57 at Pan-p o, Shensi, made of red pottery painted with black (carbon) trian es over a slip rf white clay, 12.7 cm in height, from the fifth or fourth RC. Taken from The Cienius rf China [2], 

FIGURE 1,4 Wine cup with tripod feet, afbronze, from the seventeenth century B.C. (one of the earliest so far known). Taken from Treasures from the Bronze Age of China [6]. 

Most important, this bronze vessel has seams which show it to have been cast from a mold made in four separated sections. This wine cup required a complex ceramic mold, which sets the early Chinese bronze technology apart from the lost-wax process used in the West. 

Whilst I was still seeking a difference in chemical composition [in the different crystals of the phosphate] I succeeded several times, in the recrystalUzation of the phosphate, in obtaining crystals having the same form as the acid arsenate. Since I knew definitely that there was no difference between the two salts I proceeded with the investigation of this phenomenon, and the whole solution of the acid phosphate crystallized several times in the form of the arsenate. 

Hence it is established that one and the same body, composed of the same substances in the same proportions, can assume two different forms. This is easily understood from the atomic theory different forms can result according as the position of the atoms with respect to one another is changed, but the number of different forms remains quite restricted. 

Mitscherlich s mentor, Berzelius, considered the discoveries of isomorphism and dimorphism, as it was initially called, the most important made since the doctrine of chemical proportions, which depends on them of necessity for its further development . 

Mitscherlich followed this paper shortly thereafter with another one on the dimorphism of sulphur (1822-1823). Actually, others had earlier identified more than one crystal form for a number of materials. Klaproth (1798) had recognized that calcite and aragonite have the same chemical composition and Davey had recognized that diamond was a form of carbon (Encyclopedia Brittanica 1798). This prompted Thenard and Biot (1809) to reach nearly the same conclusion as Mitscherlich, in stating that 

Monoclinic sulphur (in addition to the more common orthorhombic form) had also been recognized and documented by a number of other people (see, e.g. Partington 1952 which also contains many early references to polymorphism and polymorphic materials). 

As described in the Introductory Chapter, attention was focused [1] prior to 1961 mainly on the morphology of the cool-flame and ignition regions, rates were followed by pressure change, and essentially chemical techniques were used for product analysis. The acceptance of free radicals, followed by the masterly and elegant Semenov theory [2], which established the principles of branched chain reactions, provided the foundation for modern interpretations of hydrocarbon oxidation. This chapter builds on these early ideas, and pioneering experiments such as those carried out by Knox and Wells [3] and Zeelenberg and Bickel [4], to provide a detailed account of the reactions, thermochemistry and detailed mechanisms involved in the gas-phase chemistry of hydrocarbon oxidation. 

During the forties and early fifties, Veselovskii (1941-1952) carried out extensive investigations on AgBr/Ag and oxidised Zn, Fe, Pb, Ag, Au and Pt, confirming by measurements of spectral sensitivity and quantum yield that the observed photo- 

The use of nanoscale constructs has given a further major boost to solar photon conversion. The scale of nanosized materials such as quantum dots and nanotubes, conventionally taken to lie in the range 1-100 nm, produces very interesting size quantisation effects in optoelectronic and other properties bandgaps shift to the blue, carrier lifetimes increase, potent catalytic properties emerge and constructs with very high surface-to-volume ratios can be made. Incorporation of nanoscale structures in photovoltaic devices allows these unique properties to be exploited, with conversion efficiencies above the detailed balance limit becoming possible in principle. 

Nanosized TiOi powders are of outstanding importance in this context. Aqueous suspensions of 30 nm particulate TiOi (mostly in the rutile form) are the active agent in many of the photocatalytic systems described by Serpone and Emetine in Chapter 5. Agglomerations of Ti02 nanoparticles into mesoporous films of pore size 2-50 nm which allow the penetration of liquid are the basis of the important dye-sensitised solar cell (DSSC) discussed by Grateel and Durrant in Chapter 8, as well as most of the hybrid devices described by Nelson and Benson-Smith in Chapter 7, and some of the ETA (Extremely Thin Absorber) cells described by Konenkamp in Chapter 6. The term eta-solar cell was actually introduced by Konenkamp and co-workers (Siebentritt et al., 1997), who had earlier used the term sensitisation cell for the same type of device (Wahi and Konenkamp, 1992). Precursors to ETA cells with liquid electrolytes as hole conductors were developed by Vogel et al. (1990), Ennaoui et al. (1992) and Weller (1993). Similar electrolytic cells with RuSa (Ashokkumar et al, 1994) and InP (Zaban et al, 1998) nanoparticle absorbers have also been demonstrated. 

By the early 1990s, the basic paradigm that efficient protein folding in vivo depends on a set of highly conserved proteins termed molecular chaperones was well established (Cheng et at., 1989 Gething and 

The discovery that TCP1 is the eukaryotic chaperonin immediately raised the question of whether it also required a GroES-like co-chaperonin. While GroEL can assist the folding of some substrates in vitro without GroES, this is the case only for proteins that are also able to fold without GroEL s assistance (Martin et al., 1991 Schmidt et al., 1994) in vivo, GroES is required for life under all conditions (Fayet 

The Hspl 04/Clp Family A Connection between Proteolytic and Folding Machinery 

The heat shock response in E. coli is arguably the best studied stress response in terms of both the scope and function of its target genes (reviewed in Gross, 1996). Whole genome analysis began in earnest with 

Adjacent to Hsp33 on the chromosome is another highly conserved protein, Hspl5, which shows a 43-fold induction at high temperature, a level that is considerably greater than nearly all of the well-studied 

Supercritical carbon dioxide attracted much attention in the latter half of the nineteenth century. Dr Thomas Andrews, vice-president of Queen s 

College, Belfast, carried out an extensive investigation in the mid-1800s on the phase behavior of carbon dioxide. In his now quite famous Bakerian Lecture delivered to the Royal Society in 1869 he described his experimental apparatus (which was modified slightly by Hannay and Hogarth) and his observations of the critical properties of carbon dioxide (Andrews, 1875-76). In his lecture he related that 

On partially liquefying carbonic acid by pressure alone, and gradually raising at the same time the temperature to 88°Fahr., the surface of demarcation between the liquid and gas became fainter, lost its curvature, and at last disappeared. The space was then occupied by a homogeneous fluid, which exhibited, when the pressure was suddenly diminished or the temperature slightly lowered, a peculiar appearance or flickering striae throughout its entire mass. At temperatures above 88°[F) no apparent liquefaction of carbonic acid, or separation into two distinct forms of matter, could be effected, even when a pressure of 300 or 400 atmospheres was applied. 

The values that Dr Andrews reported for the critical point of carbon dioxide, 30.92°C and 74.0 bar, are in close agreement to presently accepted values, 31.1°C and 73.8 bar. 

In later presentations to the Royal Society, Hannay responded to Ramsay s charge, asking permission to point out some errors into which Prof. Ramsay had fallen. In addition to pointing out those errors, Hannay discussed still other experiments that later substantiated the pressure-dependent dissolving power of a supercritical fluid as a new phenomenon (Hannay, 1880). 

A chronological listing of the major advances in research into the glutathione 

1981 Proof that distinct GST subunits can hybridize, forming heterodimers Demonstration of polymorphic expression of GST in humans 

1984 First full-length cDNAs encoding GST described Expression of pi-class GST in hepatic preneoplastic nodules 

1985 Overexpression of GST in dmg-resistant cells lines Alpha-, mu-, and pi-class GST families defined 

1986 Association between absence of mu-class GST and susceptibility to lung cancer 

Hepatitis B subunit Recombivax HB , Merck Co., Inc. Vaccination against hepatitis B 

Human insulin Humilin, Eli Lilly Treatment of diabetes 

Monoclonal antibody against CD3 Orthoclone OKT , Ortho Biotech Prevention of organ rejection 

Human growth hormone Protopin , Genentech, Inc. Growth failure in children 

Human interleukin-2 Proleukin , Chiron Therapeutics Metastatic renal cell carcinoma 

It was apparent to industry representatives and the EPA that an incorrect chemical name was being used for nonylphenol (and 

So far we have mainly described perturbations (and integrations) with respect to real physical properties, such as a reaction coordinate or the temperature. However, in the section on umbrella sampling we provided several applications of theories derived by Zwanzig (Eq. [22]) and Kirkwood (Eq. [33]) for fluids that are based on nonphysical transformations of the Hamilton- 

Such transformations constitute the basis of thermodynamic cycles, which have been used extensively for evaluating the free energy of binding of ligands to an enzyme, hydration free energies of small molecules, enzymatic reactions, etc. 

Further developments of these ideas took place in computational structural biology, where nonphysical local transformations were implemented within the framework of thermodynamic cycles. These nonphysical transformations were introduced in 1981 by Warshel, who studied ionization in acidic residues in proteins pK calculations). Although the cycle included nonphysical transformations, they were not carried out by the perturbation technique. A year later Warshel used the perturbation method together with umbrella sampling to study the solvation free energy contribution to an electron transfer reaction coordinate, using two spheres for donor and acceptor in water the perturbation, however, was performed along a physical path. Warshel also modeled some enzymatic reactions that involve nonphysical processes.  

The use of nonuniform electric fields for causing useful separations of materials probably goes back to the nineteenth century, when Lowden in 1891 patented an invention for the abstraction of metallic particles from used lubricating oils. As practiced, it probably involved what we would now term mutual dielectrophoresis of the polarizable metal particles. Here the metal particle produces a distortion of the electric field about it. 

The use of alternating (ac) fields rather than static (dc) electric fields here has arisen, of course, because we are interested in dielectrophoresis effects upon neutral particles, and not in electrophoresis effects upon charged particles, such as ions. In fact this is a major point of difference between the two techniques, dielectrophoresis and electrophoresis. 

By means of DEP, investigations of biological particles such as cells or their parts have established that cells can be made to move concertedly, and in a manner directly dependent upon their individual electrical identities. 

The behavior of biological particles in uniform electric fields appears to 

The occurrence of such mysterious orientational effects in cells exposed to external electric fields caused Heller and othersto suspect the 

The structural analysis of molecular systems, especially proteins and other 

There are several excellent handbooks and texts that provide comprehensive reviews of molecular modeling methods. Noteworthy among these are Clark (1985) and Allen and Tildesley (1987), and the more recent volumes by Frenkel and Smit (1996) and Leach (1996). The recent publication by Schleyer (1998) presents an outstanding and 

The Austrian botanist Reinitzer, when heating cholesteryl benzoate, observed a melting point at 145.5 °C, leading to a cloudy liquid which cleared at a temperature of 179.5 °C. He had diseovered cholesteric liquid crystals. In 1922, FriedeE described a variety of different liquid crystal phases and proposed a classification scheme consisting of the three broad classes nematic, cholesteric and smectic materials. 

A decade ago, Olney et al. (1971) made the conceptual leap linking the neurotoxic action of the acidic amino acids to their neuroexcitatory 

The development of the steam reforming process has not been based on initial understanding of the catalysis. The progress was driven mainly by an inductive approach with feedback from industrial operation and pilot tests [417], 

The initial vague ideas about the mechanism were formulated by industrial groups around 1970 [22] [381], whereas only few academic scientists were involved in studies of the reaction. This included the groups around Temkin [58], Balandin [35], Borowiecki [36], Trimm [304] and Ross [373]. The activation of methane was studied in the 1960s by Kemball [270] by deuterium exchange studies also applied by Frennet [198]. 

Dowden (ICl) [162] [163] had ideas based on the collective properties of the solids. These ideas were strongly opposed by Sachtler who argued in terms of the properties of the individual surface atom [433] or groups (ensembles) of atoms [354]. 

The ICI group [446] thought that olefins were intermediates, but the studies were carried out at high temperatures and thus influenced by thermal cracking. Other work by Andrew [22] dealt with the function of alkali in terms of regasification. The Topsoe Group [366] [381] [384] argued that alkali promotes the adsorption of water by spill-over of water from the support to the metal surface. At the same time, early research 

The strong depressing effect of alkali on the catalyst activity was similar for the two reactions (refer to Table 6.1). It means that the retarding effect of alkali on the activity is independent of the presence of water. The impact on the activity is not related to K as discussed in Sections 3.5.2 and 4.3.1. 

Carbon, in the form of charcoal, is an element of prehistoric discovery and was familiar to many ancient civilizations. As diamond, it has been 

Chemical vapor deposition (CVD) of carbon patented 1880 Production of first molded graphite (Acheson process) 1896 Carbon dating with C isotope 1946 

Industrial production of carbon fibers from rayon 1950 s 

Development of pitch-based carbon fibers Iate1960 s 

Production of synthetic diamond suitable for gem trade 1985 Development of diamond-like carbon (DLC) 1980 s 

The original work on which subsequent study and synthesis of retinoids are based was carried out by Karrer and Morf (1933) and Heilbron et al, (1932, 1948). In 1931 Karrer et aL were able to determine the structure of retinol (1) using a highly purified vitamin A extract that they had obtained from shark liver oil (von Euler and Karrer, 1931). Using such retinol preparations, the first oily retinol esters [for example retinyl acetate (9)] were prepared (Karrer et al., 1931 Heilbron et al., 1932). 

The structure of p-carotene had been determined as early as 1930 (Karrer et ai). These two results made it possible to see from a chemical standpoint why p-carotene is a natural precursor of vitamin A compounds, a fact that had already been discovered between 1928 and 1930 in a large number of animal experiments (von Euler et al., 1929 Moore, 1930). The mechanism of the conversion of P carotene to retinaldehyde (2) was explained in detail only at a much later date (Goodman and Olson, 1969). 

In 1935 Hamano and Kawakami (1935) characterized retinol (1) as the P-naphthoate and anthraquinone P-carboxylate. Later Baxter and Robeson (1940) were able for the first time to obtain crystalline retinyl palmitate (113) and crystalline retinol (1) from liver oils. Crystalline retinyl acetate (9) and crystalline retinyl succinate were obtained at a later date (Baxter and Robeson, 1942). These very pure compounds made possible the accurate determination of a number of physical data. In 1946 Hanze et al. (1948) synthesized pure retinyl methyl ether (571) from crystalline retinol (1), and the total synthesis of this ether was reported at the same time by Milas et al. (1948). At this time also, syntheses of retinoids were carried out by Isler and associates and led to the first industrial synthesis of retinol derivatives (Isler et al., 1947 Isler, 1950 Heilbron and Weedon, 1958 Isler, 1979). 

As early as 1937 Kuhn and Morris (1937) reported the first total synthesis of a retinoid. By Knoevenagel condensation of P-C,5 aldehyde (4) with dimethyl-acrolein (5) and reduction of the product with aluminum isopropoxide, they 

The successful synthesis of (all- )-retinoic acid (3) was reported by Arens and van Dorp (van Dorp and Arens, 1946) in 1946, but almost 10 years passed before Robeson et aL (1955a) were able to prepare 13-cw-retinoic acid (17). Between 1946 and 1956, a large number of papers were published on successful syntheses of the natural C20 retinoids retinol (1), retinaldehyde (2), and retinoic acid (3), and nine industrial processes for the synthesis of vitamin A were developed during this period (Isler, 1979). 

Theoretical treatments of attractive forces between molecules (and/or atoms) in the gas phase can be traced as far back as 1873 to the efforts by van der Waals to describe the deviation of real gases from ideal behavior at relatively high densities. By the early 1930s, theoretical explanations of the origins of van der Waals attractive forces began to emerge from the likes of Keesom, Debye, Falckenhagen, and London. This body of 

As discussed in Paresegian s recent book, the modern view of dispersion interactions has its roots in the the Casimir effect. Rather than charge fluctuations, the phenomenon can be viewed in terms of zero-point electromagnetic-field fluctuations in the vacuum as allowed by the Heisenberg uncertainty principle (AEAt b/ln). Atoms and molecules can absorb some of these frequencies, namely those frequencies that are resonant with transitions between the quantum mechanical energy levels of the system as determined by its electronic structure. This absorption of the electromagnetic fluctuations gives rise to attractive forces between two bodies. 

It will become evident in later sections that the nature of the weak noncovalent interactions in a cluster dictate which computational methods will produce accurate results. In particular, it is far more difficult to compute reliable properties for weakly bound clusters in which dispersion is the dominant attractive component of the interaction. For example, Hartree-Fock supermolecule computations are able to provide qualitatively correct data for hydrogen-bonded systems like (Fi20)2 even with very small basis sets, but this approach does not even bind Ne2- What is the origin of this inconsistency Dispersion is the dominant attractive force in rare gas clusters while the electrostatic component tends to be the most important attractive contribution near the equilibrium structure (H20)2- As London s work demonstrated,dispersion interactions are inherently an electron correlation problem and, consequently, cannot be described by Flartree-Fock computations. To this day, dispersion interactions continue to pose a significant challenge in the field of computational chemistry, particularly those involving systems of delocalized n electrons.  

Fortunately, the incidence of acute disease in the United States greatly declined after the implementation of the exposure standard and reduction of beryllium levels in the workplace (11,12). Unfortunately, numerous cases of CBD continue to occur (13-34). 

Adherence to the existing standard does not afford full protection from CBD (13,17,26-30,35-37). The American Conference on Governmental Industrial Hygienists has proposed a change of the threshold limit value for beryllium to 0.02 pg/m (38). 

The 1960s witnessed the continued support of some polio patients at home, as well as the introduction of mouthpiece ventilation for long term, even continuous, support at some specialized rehabilitation hospitals (4). The 1960s also ushered in intensive care units (ICUs) that served as specialized centers to treat patients with acute respiratory failure. Sophisticated mechanical ventilators were developed to treat these patients. Some of whom failed to wean and often spent weeks or months in these units because no other facilities were available to adequately care for them. 

During the 1970s, more patients with respiratory failure due to neuromuscular disorders and chest wall deformities received long-term ventilatory assistance at home, either via tracheostomy or body ventilators, which provided effective nocturnal noninvasive ventilation (NIV) (5,6). In the 1970s, the development of home respiratory therapy companies improved support for home mechanical ventilation (HMV). Respiratory therapists could now set up ventilatory equipment, educate the patient and caregivers about using the equipment, and be available to deal with problems. 

In 1908, at the University of Leiden, Kamerlingh Qnnes succeeded in liquefying He at 4.2 K. Since this was the lowest temperature ever achieved at the time, he naturally started investigating physical properties of various materials at these low temperatures. For example, he measured the resistance of Pt down to this temperature and found that, like most good conductors, the resistivity decreased as T was lowered, and approached some finite value po as T 0. However, in 1911 when he tried Hg, much to his surprise, the resistivity suddenly dropped to 0 at aroimd 4 K. Subsequent work revealed that 27 elemental materials as well as many alloys exhibit this unusual property at very low temperatures. The elements that become superconductors are foimd in the left portion of the transition elements and in group II, III, and IV to the right of the transition elements. Also, some of the lanthanides and actinides become superconductors. Some of these are listed in Table 26.1 along with their transition temperature, Tq- 

Other elements become superconducting under pressure (e.g.. As, Ba, Ce, Ge). No alkali metals or noble metals are superconductors. Matthias pointed out that the transition temperature is generally higher if the electron per atom ratio is odd, as can be seen from the above tables (group IVA being the exception). 

Group IVB Group VB Group VIB Group VIIB Group Vin Group VIII 

Source Data from Ashcroft, N.W. and Mermin, N.D., Solid State Physics, Brooks Cole, Philadelphia, 1976. 

It was not until 1957 that the phenomena of superconductivity was explained by a theory developed by Bardeen, Cooper, and Schreiffer (BCS theory) in which it was postulated that two electrons became loosely bound by exchanging a virtual phonon (another way of saying a cooperative interaction with the lattice ions). By becoming paired with opposite spins, the so-called Cooper pairs act as bosons and are no longer controlled by the Pauli principle therefore, many can exist in the same quantum state. This pairing creates an energy gap about the Fermi level in which no states are available for the Cooper pair to be scattered into hence, they can move through the lattice unimpeded, very much like the superfluid state of liquid He which exhibits zero viscosity. 

The first known utilization of filamentons fnngi for beneficial purposes is the traditional food and beverage fermentations used in many Asian cultures. 

There are multiple drivers of our quest to obtain an improved understanding of particle-respiratoiy tract interactions. One of these is the need to devise eontrol strategies that will limit the potential for human disease from airborne materials. Another motivation is the desire to simply expand the boundaries of what is known about particles and the respiratory tract, a motivation grounded in seien-tific curiosity or our desire to explore the unknown. 

In both these cases, placing our quest for new knowledge within an overall 

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Let us continue with this same example and assume that occupational health and regulatory authorities are eager to know the inherent toxieily of this new material, even if large particles predominate at all stages of the manufaeturing process. They argue that some small respirable particles are present and eould 

Gases Mechanism Vapors determining Particles disposition Droplets in body Fibers 

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G. Deamaley, "Historical Perspective of Ion Implantation," in Proceedings 8th International Conference on Suface Modification of Metals by Ion Beams, Kanai wa, Japan, North-HoUard, Amsterdam. 

Discontinued in 1976, no fields extant included for historical perspective. ... 

K. R. BuUock, "The Development and AppHcations of Storage Batteries—Historical Perspectives and Future Prospects," in Proceedings, 7th Australian Electrochemistry Conference, 1988. 

E. J. Dowd, W. M. Sheffer, and G. E. Addison, "A Historical Perspective on the Euture of Catalytic Oxidation of VOCs," paper 92-109.03, 85th Jinnual Meeting of Air and Waste Management A.ssociation, Kansas City, Mo., June 21—26,1993. 

Rinehar, J.S., Historical Perspective Metallurgical Effects of High Strain-Rate Deformation and Fabrication, in Shock Waves and High-Strain-Rate Phenomena in Metals (edited by Meyers, M.A. and Murr, L.E.), Plenum, New York, 1981, pp. 3-20. 

IV. INTERNAL COORDINATE MOLECULAR DYNAMICS A. Main Problems and Historical Perspective... 

Fragola, J. R. 1996 Reliability and Risk Analysis Data Base Development an historical perspective. Reliability Engineering and System Safety, 51, 125-136. 

Eisenbud, M, "Environment, Technology and Health—Human Ecology in Historical Perspective." New York University Press, New York, 1978. 

A. V. Sokolov. Optical Properties ofMetaL. Elsevier, New York, 1967, Chapters 10 and 11. A very detailed, mathematical description of solutions to the wave equations, with a nice historical perspective. 

Regarding a historical perspective on carbon nanotubes, very small diameter (less than 10 nm) carbon filaments were observed in the 1970 s through synthesis of vapor grown carbon fibers prepared by the decomposition of benzene at 1100°C in the presence of Fe catalyst particles of 10 nm diameter [11, 12]. However, no detailed systematic studies of such very thin filaments were reported in these early years, and it was not until lijima s observation of carbon nanotubes by high resolution transmission electron microscopy (HRTEM) that the carbon nanotube field was seriously launched. A direct stimulus to the systematic study of carbon filaments of very small diameters came from the discovery of fullerenes by Kroto, Smalley, and coworkers [1], The realization that the terminations of the carbon nanotubes were fullerene-like caps or hemispheres explained why the smallest diameter carbon nanotube observed would be the same as the diameter of the Ceo molecule, though theoretical predictions suggest that nanotubes arc more stable than fullerenes of the same radius [13]. The lijima observation heralded the entry of many scientists into the field of carbon nanotubes, stimulated especially by the un-... 

Tanner, R.I. and Walters, K. (1998) Rheology An Historical Perspective (Elsevier Amsterdam). 

Lewis, D. J. 1980. Unconfined vapor cloud explosions—Historical perspective and predictive method based on incident records. Prog. Energy Comb. Sci., 1980. 6 151-165. 

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