Susan B. Masters PhD

• Associate Dean, School of Medicine
• Professor of Pharmacology Department of Cellular & Molecular Pharmacology
• University of California, San Francisco

https://profiles.ucsf.edu/susan.masters

It is involved in numerous intracellular cell signalling and energy transfer processes erectile dysfunction organic purchase malegra fxt plus 160mg amex. Thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters impotence from priapism surgery discount malegra fxt plus 160mg with mastercard. A 646 amino acid heat shock cognate protein functioning as a molecular chaperone erectile dysfunction treatment in urdu order malegra fxt plus 160mg visa, facilitating the folding of other cellular proteins erectile dysfunction cvs purchase 160 mg malegra fxt plus with visa. It plays an important role in cells by transiently associating with nascent polypeptides to facilitate correct folding doctor for erectile dysfunction in ahmedabad buy discount malegra fxt plus 160mg line. Families of proteins conserved through prokaryotic and eukaryotic cells and bacteria in response to hyperthermia and other environmental stresses erectile dysfunction doctor atlanta purchase malegra fxt plus 160 mg free shipping, although some are constitutively expressed erectile dysfunction cycling order malegra fxt plus 160 mg online. They increase thermal tolerance and perform functions essential to cell survival under these conditions erectile dysfunction treatment sydney 160mg malegra fxt plus overnight delivery. Any of a group of proteins that are produced especially in cells subjected to stressful conditions (as high temperature), that serve to ensure proper protein folding, and that are held to comprise a class of molecular chaperones. A long-chain fatty acid that is henicosane in which one of the methyl groups has been oxidised to give the corresponding carboxylic acid. Hemagglutinins may be in the form of antibodies, viral capsid proteins, or certain plant lectins. The volume percentage of erythrocytes in whole blood; also, the apparatus or procedure used in its determination. There are four heme groups in a hemoglobin molecule, each consisting of a cyclic structure of four pyrrole residues, called protoporphyrin, and an atom of iron in the center. Blue, oxygen transporting, copper containing protein found in the blood of molluscs and crustacea. A glycoprotein that binds heme preventing its excretion in urine and that is part of the betaglobulin fraction of human serum. It is always found within cells (as opposed to circulating in blood) and appears to be a complex of ferritin, denatured ferritin and other material. The iron within deposits of hemosiderin is very poorly available to supply iron when needed. Palmitate, also called n-hexadecanoate, is the dissociated and observed form of Palmitic Acid at physiological pH A barbiturate C12H16N2O3 used as a sedative and hypnotic and in the form of its soluble sodium salt C12H15N2NaO3 as an intravenous anesthetic of short duration. Hexoses include Fructose, Fucose, Galactose, Glucose, Mannose, Rhamnose, and Sorbose the serum cholesterol carried on high-density lipoproteins, approximately 20 to 30 per cent of the total. It induces capillary dilatation, which increases capillary permeability and lowers blood pressure; contraction of most smooth muscle tissue; increased gastric acid secretion; and acceleration of the heart rate. Acts as a proton donor or acceptor and has high potential reactivity and diversity of chemical function. Homocysteine is a thiol-containing amino acid formed by a demethylation of methionine. An acid that is produced by normal metabolism of dopamine and may be elevated in the urine in association with tumors of the adrenal gland. The ratio of Homovanillic acid to Dopamine found in a sample A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. A high urinary level is found in progeria Organic compounds composed exclusively of carbon and hydrogen where no carbon atoms join to form a ring structure. This enzyme has a ferrous ion at the active site and a reducing agent such as ascorbate is necessary to maintain the iron in the ferrous state. The presence of hydroxyproline is essential to produce stable triple helical tropocollagen, hence the problems caused by ascorbate deficiency in scurvy. This unusual amino acid is also present in considerable amounts in the major glycoprotein of primary plant cell walls. Plasma membrane protein of unknown function, predicted to be palmitoylated; has similarity to hydrophilins, which are hydrophilic, glycine-rich proteins involved in the adaptive response to hyperosmotic conditions. A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. A plasma and urinary tryptophan-related metabolite related to metabolic and skin diseases. Also: 3-Indolebutyric acid, Indole-3-butyric acid, Indole-3-butanoic acid/ en. A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It is structurally different from type I interferon and its major activity is immunoregulation. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene. Its biological effects include the ability to replace macrophage requirements for T-cell activation, as well as affecting a wide range of other cell types. Interleukin-10 is a cytokine produced by a variety of cell types, including T-lymphocytes; monocytes; dendritic cells; and epithelial cells that exerts a variety of effects on immunoregulation and inflammation. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by dendritic cells; macrophages and a variety of other immune cells and plays a role in the stimulation of interferongamma production by T-lymphocytes and natural killer cells. It binds to the interleukin-12 subunit p35 via a disulfide bond to form interleukin-12 and to interleukin-23 subunit p19 to form interleukin-23. Interleukin-1 alpha is an interleukin-1 subtype that occurs as a membranebound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike Interleukin-1beta both membrane-bound and secreted forms of interleukin-1alpha are biologically active. It stimulates the growth of certain disease-fighting blood cells in the immune system. Interleukin 2 also increases the proliferation and maturation of the cd4 cells themselves. Interleukin-3 is a multilineage cell growth factor secreted by lymphocytes; epithelial cells; and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. It also acts on Tlymphocytes, mast cells, and several other hematopoietic lineage cells. An interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. A subclass of iridoid compounds that include a glycoside moiety, usually found at the C-1 position. A rare amino acid found in elastin, formed by condensation of four molecules of lysine into a pyridinium ring. Chemical name: Pyridinium A desmosine cross-link is formed from three allysyl side chains plus one unaltered lysyl side chain from the same or neighbouring polypeptides. A ferulic acid consisting of trans-cinnamic acid bearing methoxy and hydroxy substituents at positions 4 and 3 respectively on the phenyl ring. Any of various usually hydroxyl derivatives of isoflavone that are plant compounds possessing antioxidant and estrogenic activity in the body. An amino acid that occurs in most dietary proteins and is essential for proper growth in infants and for nitrogen balance in adults. Measure of the ability of an insoluble material to undergo displacement of ions previously attached and loosely incorporated into its structure by oppositely charged ions present in the surrounding solution. In such a reaction the isotope distribution tends towards equilibrium (as expressed by fractionation factors) as a result of transfers of isotopically different atoms or groups. A protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constituitively associated with the prolactin receptor and is required for responses to gamma interferon. Regulated plant growth and development processes include growth inhibition, senescence, tendril coiling, flower development and leaf abscission. It has an important role in response to wounding of plants and systemic acquired resistance. An overabundance of ketones in the bloodstream is seen in a severe metabolic derangement known as diabetic ketoacidosis. Resin-like substance secreted by certain lac insects; used in, for example, varnishes and sealing wax. Lactate is a product of fermentation and is produced during cellular respiration as glucose is broken down. The ratio of lactate to pyruvate found in a sample A colorless or yellowish, syrupy, water-soluble liquid, which is a byproduct of anaerobic glucose metabolism. An intermediate product of carbohydrate metabolism (anaerobic metabolism), derived chiefly from muscle cells and red blood cells. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Other names Vitamin C; L Ascorbic Acid; Ascorbate, Sodium; Ascorbate, Ferrous; Acid, L-Ascorbic; Acid, Ascorbic; Sodium Ascorbate; Magnorbin; Magnesium Ascorbicum; L-Ascorbic Acid; Hybrin; Ferrous Ascorbate; Ascorbic Acid, Monosodium Salt. Aspartic acid has an overall negative charge and plays an important role in the synthesis of other amino acids and in the citric acid and urea cycles. The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Also: Levodopa, 3 Hydroxy L tyrosine, 3-Hydroxy-L-tyrosine, Dopaflex, Dopar, L 3,4 Dihydroxyphenylalanine, L Dopa, L-3,4-Dihydroxyphenylalanine, L-Dopa, Larodopa, Levopa. The L form of glutamine, a non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. The L form of isoleucine, an essential branchedchain aliphatic amino acid found in many proteins. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. The L form of leucine, an essential branchedchain amino acid important for hemoglobin formation. The L form of proline, a cyclic nonessential amino acid in humans (synthesized from glutamic acid and other amino acids). It is a constituent of many proteins and is found in high concentrations in collagen. Sugar acids are compounds containing a saccharide unit which bears a carboxylic acid group. The L form of threonine, an essential amino acid occurring naturally in the L-form, which is the active form. The L form of Tryptophan, an essential amino acid that is the precursor of both serotonin and melatonin. The L form of valine, a branched-chain essential amino acid that has stimulant activity. Lauric acid, dodecanoic acid (C12:0), a crystalline fatty acid occurring as glycerides in natural fats and oils, especially coconut oil and palm-kernel oil. The content of Lead Iodine found in an organism or tissue, including radiolabeled ions. A red iron-containing protein, similar in a number of properties to the hemoglobin of blood, that forms in the root nodules of actively nitrogen-fixing leguminous plants of the genus Leguminosae. Leghemoglobin is a product of the symbiosis of two organisms: it consists of a heme synthesized by nodule bacteria and a globin formed by the cells of a higher plant. Leghemoglobin is destroyed when the nodules lose their capacity for symbiotic nitrogen fixation. A white crystalline amino acid occurring in proteins that is essential for nutrition; obtained by the hydrolysis of most dietary proteins. The leucocrit value expresses the leucocyte volume in relation to the total volume of blood. The leucocrit value is determined in heparinized microcapillaries simultaneously with the determination of the haematocrit value. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). Organic substance which act as a binder for the cellulose fibres in wood and certain plants and adds strength and stiffness to the cell walls. A crystalline fatty acid C24H48O2 that is found especially in wood tar (as from beechwood) and in the form of esters in many fats, fatty oils, and waxes and is derived from kerasin. A hydrocarbon; liquid terpene with a lemon odor; found in lemons and oranges and other essential oils; a chiral molecule. A colorless, fragrant liquid, C10H18O, distilled from the oils of rosewood, bergamot, and other plants and trees and used in perfume manufacture. Linolenic acid (C18:3n-3), also C18:3 (all cis9,12,15) acid or alpha-Linolenic acid, is a poly unsaturated fatty acid. Linolenic acid - One of the principle unsaturated fatty acids in plants and essential fatty acids in plants and an essential fatty acid in animal nutrition. Any of a group of organic compounds, including the fats, oils, waxes, sterols, and triglycerides, that are insoluble in water but soluble in common organic solvents, are oily to the touch, and together with carbohydrates and proteins constitute the principal structural material of living cells. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin e, structural separation or low oxygen tension. In an aqueous system, the polar heads of lipids align towards the polar, aqueous environment, while the hydrophobic tails minimize their contact with water and tend to cluster together, forming a vesicle; depending on the concentration of the lipid, this biophysical interaction may result in the formation of micelles, liposomes, or lipid bilayers. Micelles and bilayers form in the polar medium by a process known as the hydrophobic effect. Lipofuscins are lipogenic pigments found chiefly in the smooth muscle cells, heart muscle cells, macrophages, parenchyma cells, interstitial cells, nerve cells, and ganglion cells. An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of Linoleic acid and is a coenzyme of oxoglutarate dehydrogenase. Also: lipoate, Heparlipon, R-(+)alpha-Lipoic acid, (+)-alpha-Lipoic acid, and (R)(+)-1,2-Dithiolane-3-pentanoic acid. A complex of lipids and apolipoproteins, the form in which lipids are transported in the blood. Lipoprotein substances (combination of a fat and a protein) which acts as a carrier for cholesterol and fats in the bloodstream. High levels of low density lipoprotein are considered a positive risk factor for the development of coronary artery disease. Less than 130 mg/dl is desirable, 130 to 159 mg/dl is borderline high, over 160 is considered high. A red crystalline substance, C40H56, that is the main pigment of certain fruits, as the tomato and paprika, and is a precursor to carotene in plant biosynthesis. They result from partial hydrolysis of phosphatidylcholines which removes one of the fatty acid groups. Lysophosphatidylethanolamine is a specific inhibitor of phospholipase D, a key enzyme in the degradation of membrane phospholipids during the early stages of plant senescence. By this action, it retards the senescence of leaves, flowers, and post-harvest fruits. Lysophosphatidylglycerol, with a fatty acid in position sn-1 only, has been reported to have some biological properties in animal tissues in vitro, but it is not known whether these are relevant in vivo. A chemical element, its salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Malondialdehyde is reactive and potentially mutagenic has shown to be found in heated edible oils such as sunflower and palm oils. A chemical element, its salts occur in the body tissue in very small amounts and activate liver arginase and other enzymes. A white, crystalline, water-soluble, slightly sweet alcohol that is used as a dietary supplement and dietetic sweetener and in medical tests of kidney function. Mannitol occurs naturally as an important food storage and transportation molecule in brown algae like kelp. Among microalgae, the marine diatom Haslea ostrearia has the distinctive feature of synthesizing and releasing, into the surrounding environment, a blue-green polyphenolic pigment called marennine. The oyster-breeding industry commonly makes use of this natural phenomenon for the greening of oysters. Marennine exists in two different forms, the intracellular and extracellular forms. Mead Acid (C20:3n-9), also all cis-5,8,11eicosatrienoic acid, is a poly unsaturated fatty acid. The average volume of red blood cells in erythrocyte indices, calculated from the hematocrit and the red blood cell count. If the platelet count is normal, the mean platelet volume can still be too high or too low. Melanin is a class of compounds found in plants, animals, and protists, where it serves predominantly as a pigment. A precursor to the important tanning agent Lerythrulose and an aliphatic poly-alcohol used in the chemical analysis of the reactivity of various radicals and radical anions. A family of low-molecular-weight, cysteine-rich proteins present in various tissues, which bind functional.

When the frames are full of mash the gas vents are closed while mash is still being transferred into the frames erectile dysfunction song trusted 160mg malegra fxt plus. The taps or outlets from the plates are opened and the wort erectile dysfunction cleveland clinic generic malegra fxt plus 160mg amex, which has escaped through the filter cloths testosterone associations with erectile dysfunction diabetes and the metabolic syndrome cheap 160 mg malegra fxt plus overnight delivery, is recirculated to the mashing vessel until it is clear and then is collected erectile dysfunction medication costs discount 160mg malegra fxt plus amex. In older mash filters the flow of wort from each plate was regulated through individual taps leading to swan necks impotence 22 year old malegra fxt plus 160mg, which delivered the wort into a wort collection trough or grant erectile dysfunction vs impotence buy malegra fxt plus 160 mg online. After the first wort has been collected the sparge liquor male erectile dysfunction pills malegra fxt plus 160 mg with amex, which may have been rendered oxygen-free impotence world association buy generic malegra fxt plus 160 mg line, is admitted into the tops of alternate plates, displacing the wort downwards. When all the wort has been driven out, the wort outlets from these plates are closed while those of the remaining plates are opened. Now the sparge liquor passes from the first plates across through the mash in the frames and out from the second plates. When sparging has been sufficient the last of the sparge liquor is driven through the spent grains by a top pressure provided by compressed air, which also drives out the last of the spargings. These units are made of reinforced polypropylene, and a filter press consists of only this single type of unit, together with appropriate end plates, supported on a frame. When the units are assembled the space between the filter cloths is the mash chamber while the spaces between the cloths and the transverse partitions of the plates make up the wort collection chambers and the sparge inlets and outlets. The plates are opened in the usual way to discharge the spent grains which separate from the two filter cloths. The use of an air purge at the end of sparging gives relatively dry spent grains, with ` 74% moisture. The worts are concentrated, extract recoveries equal laboratory yields and the cycle time is less that 120 min. Like other newer filters made primarily of polypropylene, heat losses are less Recessed chamber plate Filter cloth. The spent grains were discharged by unsealing the bases of the pockets which are sealed by pressure against the groove on the metal plates. The bold arrows indicate the direction of compression used on the filter assembly. This filter consisted of a set of polyester or polypropylene filter pockets, which could be opened or closed at the base, alternating with metal plates vertically grooved on one side and with a recess involved with bag closure and sealing on the other. The bags were filled from above and, after a short re-circulation period for clarification, the wort was collected. Extract recoveries were good, the worts were concentrated and the turn-round time was rapid, about 70 min. The filter is made of alternating chamber modules with membranes and plates, which are covered with filter cloths. Compression and gaskets seal between the units and create the necessary channels for the mash, wort, spargings, etc. The space between a membrane and a filter cloth, which holds the mash, is about 4 cm (1. The filter is pre-warmed and then mash is pumped into the chambers from below, while the air is vented. When the chambers are full the vents are closed, the wort outlets are opened, wort collection begins and mash delivery is continued until all the mash is in the chambers. During this process a filter-layer of solids quickly builds up on the filter cloth and the wort becomes bright so quickly that re-circulation is rarely needed. Squeezing improves the homogeneity of the bed, as well as making it thinner, and so improves the efficiency of sparging. When sparging is complete the liquor inlets are closed and the mash is compressed a second time, by inflating the membranes with compressed air (0. The plates and frames are automatically separated in turn and the spent grains fall into a receiving trough with a conveyor. These filters have rapid turn-round times, allowing 12 cycles/24 h, the worts are strong and extract recovery is exceptional, often 101 and even 103% of the laboratory value (Table 6. It has been claimed that the loading can be reduced to 70% of normal, but practical difficulties have been noted even at loadings reduced to 85% of the standard value. This filter copes well with a wide variety of grists, including those containing mostly unmalted sorghum or roasted and flaked barley. Filters are cleaned regularly by rinsing and more completely, say weekly, using caustic cleaning agents and possibly hydrogen peroxide. As with other polypropylene filters the heat loss is much less than with the older, metal filter presses. The filters consist of alternating membrane and chamber plates, mostly made of polypropylene. When the units are assembled and pressed together the edges of the cloths seal (replacing gaskets) and create mash chambers bounded on both sides by filter cloths, so wort can escape from both sides of the mash. For the production of traditional beers it may be imperative to continue using near-isothermal mashing in a mash tun or decoction mashing to retain the character of a product. For small traditional breweries making ales a mash tun, with its simple construction and low maintenance requirements, serves well if not more that two to three brews ervery 24 hours are required. For larger breweries, making large volumes of single beers, the economic advantages of using all the brewing equipment for as much of the week as possible, and making as many brews every 24 hours as possible are very great. Because both conversion and wort separation occur in 218 Brewing: science and practice Mash 1st wort (a) (b) Mash 1st wort Air Sparge liquors 1st wort (c) (d) Spargings 6 Mashing technology Air 219 Sparging (e). In the next stage the filter is opened and the spent grains fall into a collection trough and are conveyed away. A mash filter using hammer milled grist will give a better extract recovery, a more concentrated wort, drier spent grains, use less water and generate less effluent, but is likely to be more costly than a lauter tun of equivalent capacity. If the brewery is making a variety of beers that necessitate the use of different brew lengths then the greater flexibility of the lauter tun becomes decisively important. Furthermore, the use of a comparatively coarsely ground grist, suited to a lauter tun, may be needed to retain the character of a particular beer. Lauter tuns are likely to be less expensive than newer types of mash filters and require less maintenance and fewer replacements. Flexibility may be increased by having mash conversion vessels of different 220 Brewing: science and practice A A Wort 1 Wort 1 A (a) Sp L Sp (b) L (c) Sparge A (d) (e) (f). At the end of this sequence the filter is opened and the draff falls into a collecting trough. Alternatively, when slow mash conversions occur, for example because relatively high concentrations of slow-converting mash adjuncts are used, two mash conversion vessels may alternately deliver mash to a single wort separation unit. With the proposed dynamic disc mash filtration technique the rotating disc drives the mash tangentially to the filtration surface and the wort is membrane filtered. In the Pablo system the wort is separated from the mash with two, double stage decanting centrifuges, in the Reiter system a rotary vacuum filter is used and gives a high extract recovery. Other devices tried include vibrating screen filters, vibrating membrane filters, horizontal and inclined belt filters, with or without suction, cross-flow filters, Archimedean screws working in slotted casings and cyclones. Many of these methods were intended to be used with fractionated malt grists lacking husk materials so that relatively little draff would remain after the conversion process. Some were used for short periods but many did not pass beyond the experimental stage. During the period 1955 to 1975 there was intense interest in continuous brewing, with its advantages of relatively compact, continuously operating equipment with its steady demand for services and its predicted uniform product quality. Large production plants were constructed and used but many problems were encountered that led to them being replaced by batch production units. At the present time continuous fermentation is carried out on an industrial scale by only one company in New Zealand (Chapter 14) and this is not linked to continuous wort production. However, there is a revival of interest in continuous fermentation and conditioning using immobilized yeasts and this may lead back to an interest in continuous mashing, since processing is most advantageous when all stages are continuous (Briggs et al. In this equipment the mash travelled, in sequence in plug flow, through stainless steel tubes Flake Roast Malt Hot water Mash mixer Flake weigh feeder Malt weigh feeder Mill Hot water in Steam Converter tank Hot water returned Hot water Empty wash Re-circulation Prefill fill Condensate Wort out Mash filter Re-circulation Recycle Recycle Recycle. The converted mash was loaded into one of eight mash buckets, each of which resembled a small mash tun. For two hours a tun moved around a central support, occupying each of 16 positions in turn, for 15 min. The positions were used for filling, wort recycling, collection and sparging, spent grain discharge and cleaning, then return to the filling position. It is best for the brewer and the user that the draff is reasonably dry and certainly not seeping liquid. Drier draff reflects better extract recovery for the brewer and smaller transport costs and storage problems for the user. The wet state of the draff from Strainmasters was a major factor in replacing them with other equipment. Conversely, the low moisture content of the draff from mash filters is a factor in their favour. The production of dry draff becomes even more important where local conditions dictate that it must be thoroughly dried. Spent grains are usually moved by helical screw or compressed air conveyors to storage bins which typically discharge their contents directly into lorries. This area of the brewery must be regularly cleaned, since many microbes multiply on wet grains and drainings, so these represent potential sources of contamination and product spoilage. In a mash the viscosity will depend on the concentration and nature of the wort and the temperature. The porosity of the bed is more important than that of the support, the false bottom of a mash or lauter tun or the clean filter cloth of a mash filter, and is proportional to the mean diameter squared of the grist particles. Thus the finer the grind of the grist, the smaller the particles and the greater the resistance to flow. The faster flow of lauter tuns relative to mash tuns is achieved (despite the finer grists used) by reducing L, the bed depth, and this process is carried further in mash filters. As wort separation proceeds so the bed of grains builds up to a maximum thickness, L, and may then decrease as the bed contracts or is compressed. After the first wort is collected and sparging begins wort concentration and hence its viscosity, falls. The flow through the bed is proportional to the square of the mean diameter of the pores. As sparge liquor moves into the bed of grist it displaces the wort from between the particles and leaches extract from within them. The solid phase mass transfer coefficient, K G D/d where D is the diffusion coefficient and d is the diameter of the particle. Thus, the smaller the particle the greater the surface/volume ratio and the shorter the distances from points within the particle to the surface and the faster extract can be leached from it. Leaching takes time and sparging too rapidly results in inadequate leaching and a reduced recovery of extract. Since leaching is favoured by a finely ground grist while flow rate is favoured by larger particles, in practice, a compromise grist particle size must be sought for each type of wort separation equipment. The more brews/day that are required the lower the loading on a lauter tun must be. During the movement of sparge water through the mash bed there is a progressive leaching of soluble substances from within the particles and a gradient of wort concentration is established, which increases downwards through the bed. The theoretical stages are, firstly, the diffusion of extract from the interiors to the surfaces of the grist particles and, secondly, the movement of the extract into the liquid between the particles and its removal with this flowing liquid. Leaching has been approximately described by equations based on the number of theoretical washing stages involved (Table 6. More washing stages are required to minimize losses in the preparation of strong worts. Greater retention of liquor in the spent grains leads to greater losses of extract and the need for more extensive washing. As grain beds become more free running so the washing efficiency decreases and there is a tendency for extract recovery to decline. It follows that increasing the rate of sparging carries with it the risk of a significant fall in extract recovery. As previously noted with some plant, like the Strainmaster, the losses of extract in wet spent grains can be so high that it is desirable to recover the extract from the grain pressings, with the extra cost and effort involved and the risk of reducing product quality. Another process that occurs during wort separation is the filtration of the fine particles from the wort. The large bed depths used in mash tuns ensure that, combined with wort re-circulation, very clear worts can be obtained. The haziness of worts is also influenced by the grist composition and is probably increased by attempts to collect worts too fast, at rates that exceed the optima of the different pieces of equipment. Thus, as predicted, the larger the filtration area /unit mash the faster extract collection. Wort recovery from the mash tun with medium depth and an all-malt grist is complete (97% extract recovery) in 255 min. The performance (true filtration efficiency) of the Stainmaster and the lauter tuns was not as great as predicted on theoretical grounds, possibly because, at least in part, the mash beds were compressed (Harris, 1971). Many herbs were used in attempts to prolong the shelf-life of such ale (Johnstone, 1997; Behre, 1999) but only the hop, Humulus lupulus L. Detailed information about hops is found in a book by Neve (1991) and an earlier book by Burgess (1964). Hops are grown throughout the world, as illustrated in the Hop Atlas (Barth et al. Hops of commerce are the dried cones of the female plant but today much of the crop is processed into pellets and extracts. Although hops were probably used first for their preservative value, they introduced bitterness and a pleasant flavour, which was liked, and which is the reason for their continued use. These flavours were found to originate mainly in the resins and essential oils found in the lupulin glands of the hop. Humulus and Cannabis are the only two genera in the family Cannabinaceae; some authorities classify them in the Moraceae. There are some chemical similarities between hops and hashish but the resins of the two species are distinct; those of hops provide the bitter principles of beer while those of Cannabis include the psychotomimetic drug, tetrahydrocannabinol. The hop is a perennial climbing plant; the aerial part dies off in the autumn but the rootstock stays in the soil, sometimes for many years. In the wild, hops are found in hedgerows but for cultivation they are trained up strings attached to permanent wirework. In the spring the stem tissue in the upper part of the rootstock produces numerous buds from which many shoots develop. The cones consist of a central strig with bracts and 7 Hops 229 (c) (d) (e) (a) (e) 1 cm Bract scar (f) Stipular bract Bracteole (f) 1 cm Fruit (seed) Lupulin glands (g) (b) 0. Most of the lupulin glands are formed at the base of the bracteoles but they are readily detached and adhere to the bracts, strig and seed. A few lupulin glands are found on the undersides of hop leaves but not enough to make these useful for brewing. It is predicted that the maximum lupulin content/cone that could be obtained by breeding is about 32% w/w which corresponds to a () content of about 23% of the cone (Likens et al. Male flowers have five sepals and five anthers but since the flowers drop off after flowering any brewing value is lost. However, the male flowers produce pollen which can be carried long distances by the wind so any female plant in the vicinity will be fertilized and produce seeds at the base of the bracteoles. It was shown in England, as long ago as 230 Brewing: science and practice 1908, that the yield/acre was higher if the hops were fertilized so English growers were encouraged to plant male hops in their gardens and by now many are wild in the hedgerows. In contrast, in Germany, except in breeding stations, male hops must be removed by law. For example, a commercial yield of the variety Fuggle could not be obtained in the absence of male hops the bulk of the English hop crop contains seeds in excess of the European limit but in isolated areas male hops have been removed and the crop grown seedless. The hop plant is usually diploid with 20 chromosomes but triploid plants have been bred which are very infertile and have a low level of seeds even when pollinated. They require at least 13 hours of daylight for vegetative growth to occur; with shorter periods the plant becomes dormant.

Influence of Portagen and Pregestimil on essential fatty acid status in infantile liver disease erectile dysfunction drugs and alcohol generic 160 mg malegra fxt plus otc. Resting energy expenditure is increased in infants and children with extrahepatic biliary atresia erectile dysfunction doctors in san fernando valley malegra fxt plus 160mg with amex. Body composition and components of energy expenditure in children with end stage liver disease impotence antonym purchase malegra fxt plus 160mg line. Nutritional support in children with end stage liver disease: a randomised crossover trial of a branched chain amino acid supplement erectile dysfunction causes prostate cancer cheap malegra fxt plus 160 mg visa. Taylor R et al Combined sugar absorption test in children with portal hypertension impotence synonym malegra fxt plus 160mg amex. Pre-operative nutritional support in children with end-stage liver disease accepted for liver transplantation: an approach to management erectile dysfunction jackson ms buy generic malegra fxt plus 160mg. Percutaneous endoscopic gastrostomy for continuous feeding in children with chronic cholestasis erectile dysfunction at 25 cheap 160mg malegra fxt plus with visa. Essential fatty acid status in children with cholestasis top erectile dysfunction doctors new york cheap malegra fxt plus 160mg otc, in relation to serum bilirubin concentration. Effects of liver transplantation on long-chain polyunsaturated fatty acid status in infants with biliary atresia. Lochs H, Plauth M Liver cirrhosis: rationale and modalities for nutritional support. Metabolic clearance of fat emulsion containing medium chain triglycerides in cirrhotic patients. Stevenson R Nutritional intervention and growth in infants with biliary atresia in the first year. Effect of ursodeoxycholic acid therapy on hepatic function in children with intrahepatic cholestatic liver disease. Isolated liver transplant and sequential small bowel transplantation for intestinal failure and related liver disease in children. Enteral feeding improves nutritional status in cystic fibrosis patients, with liver disease. Benifla M, Weizman Z Acute pancreatitis in childhood: analysis of literature data. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Experience of nasojejunal feeding in a cohort of children with acute pancreatitis. The incidence of type 1 diabetes in children is increasing at the rate of 2% per annum and in Scotland stands at 26 per 100 000 population per year in the under 15-year-old age group [1]. The prevalence of childhood onset type 1 diabetes has increased in most western countries [2]. It is primarily a hormone deficiency disease, caused by auto-immune destruction of the pancreatic islet cells. This team should include a paediatrician, a diabetes nurse specialist and a paediatric dietitian, and should have access to psychological services and social workers in addition to services offered in primary care. The team should work collaboratively to educate and support the child and their families, while empowering them to manage diabetes on a day-to-day basis. The parents of a child who is diagnosed as having a chronic disease (including a newly diagnosed diabetic child) are initially shocked and devastated. Parents can also feel a sense of guilt: they may feel that their child has developed diabetes because they have permitted him or her to eat sweets excessively. It is vital to develop a rapport with the family so that a high quality of consistent dietetic care can be provided. Frequent and short teaching sessions are preferable, with the entire family if appropriate. First hand knowledge of the domestic set up enables teaching to become more learner centred. The disadvantages are that these sessions are costly in terms of travelling time and resources. Children with diabetes have the same basic nutritional needs as their non-diabetic 164 Clinical Paediatric Dietetics 2 3 4 counterparts. To contribute towards optimising blood sugar levels and hence ideal HbA1c (glycosylated haemoglobin) results of <7. Children should be offered the most appropriate insulin preparation for the individual. The amounts and timing of carbohydrate containing foods eaten are significant and should balance the effects of the injected insulin. It is imperative to aim to maintain blood glucose concentrations close to the normal range to decrease the frequency and severity of long term microvascular and cardiovascular complications [6]. Recurrent episodes of hypoglycaemia are undesirable, particularly in young children where the developing brain may be particularly susceptible. Dietary energy should be sufficient for growth and allow for variable exercise patterns, but should not provoke obesity. Growth should be plotted at regular intervals using standard height and weight charts. Growth velocity charts and body mass index are useful for anticipating the onset of obesity or stunting. Growth can be a useful indicator of diabetic control, as poor physical development may be a consequence of inadequate diabetic management. Obesity is less of a problem in diabetic children than in diabetic adults, but if children do gain weight disproportionately to their height, suitable dietetic advice should be given at a very early stage. Particular care should be taken to monitor the weight of adolescent girls, as this group is most prone to obesity [7] because they reach adult stature before their peers and generally take less exercise than boys. The diet should minimise the development of diabetic complications such as cardiovascular and microvascular disease. If insufficient carbohydrate is allowed then children will tend to compensate by eating more protein and fat containing foods, which is undesirable. The latter outlines the most recent consensus based recommendations for people with diabetes and there are significant changes from the earlier guidelines: greater flexibility in the proportions of energy derived from carbohydrate and monosaturated fat, relaxation in the amount of sucrose permitted and promotion of foods with a low glycaemic index. The recommendations recognise that the energy distribution between carbohydrate, fat and protein will differ depending on age: breast fed infants will obtain approximately 55% energy from fat, 7% from protein and 40% from carbohydrate, whereas a 5-year-old may derive 35% energy from fat, 15% from protein and 50% from carbohydrate. An increase in carbohydrate, particularly from high fibre sources, and a reduction in saturated and polyunsaturated fat are recommended. This is of major importance in order to minimise the risk of chronic degenerative disease such as obesity and coronary heart disease. Carbohydrate the current recommendation for the child with diabetes is that carbohydrate provides more than 45% energy. The formula: 120 g carbohydrate plus 10 g Diabetes Mellitus 165 for every year of life reflects current thinking and provides a baseline of daily carbohydrate that should provide at least 40% energy from carbohydrate. For example, this formula suggests that a 2-year-old boy should have 120 g + 20 g (140 g) carbohydrate daily. His estimated average energy requirement is 1190 kcal; hence a minimum of 47% energy will be derived from carbohydrate. It should be noted, however, that the dietary reference values for food energy [12] were not designed for the individual but for groups. A 5-year-old boy growing along the second centile will weigh 15 kg, while a boy growing along the 98th centile will weigh 24 kg. The amount of carbohydrate eaten has a greater influence on glycaemia than the source or type [13], nevertheless, many factors affect the glycaemic response to food: the amount of carbohydrate eaten, the composition of the carbohydrate, the effects of cooking or processing, and other foods eaten along with the carbohydrate. Foods containing soluble fibre should be encouraged as they have beneficial effects on carbohydrate and lipid metabolism. Insoluble fibrous foods, although they have no such effects, are advantageous to gastrointestinal health and have a high satiety factor and may benefit those trying to lose weight. Gradual changes in fibre intake are necessary to minimise colic, flatulence and abdominal distension. High intakes can impair the absorption of calcium, iron and zinc because of the high level of phytate in high fibre foods, although it can be argued that these foods themselves, being less refined, have a higher vitamin and mineral content than lower fibre foods. However, children can safely include a number of high fibre foods in their diet. A large proportion of children will eat at least two portions of fruit each day; many do not like vegetables, but will take them when included in soups and stews. The five portions of fruit and vegetables per day that is recommended for all should be particularly endorsed. Sugar It is now accepted that up to 10% of daily energy may be provided from sucrose with the stipulation that it is eaten within the context of a healthy diet. The use of sugar taken as part of a mixed meal does not have a detrimental effect on blood sugar control in well-controlled insulin dependent diabetics who are not obese [14,15]. It is also recognised that the rate of absorption of carbohydrates depends on a great many factors, and the idea that sucrose always causes a rapid rise in blood sugar is perhaps too simplistic. Rapidly absorbed carbohydrate such as a chocolate biscuit can be included in the dietary allowance at the end of a main meal, when the glycaemic response will be lower. Fish, especially oily fish, containing n-3 polyunsaturated fat should be eaten once or twice 166 Clinical Paediatric Dietetics per week. This advice should only be given to children with a high fat intake or a high weight gain. A supplement of vitamins A and D should be considered for children under the age of 5 years who are taking skimmed milk Sweeteners Nutritive sweeteners have no proven advantage over sucrose. Although it does not require insulin for its metabolism it has a glucose sparing effect in the body and causes a rise in blood sugar if large quantities are taken. They are poorly absorbed and can cause osmotic diarrhoea, particularly in children, who have a lower body mass than that of the adult, for whom the products are designed. Non-nutritive sweeteners can be useful in drinks and desserts and to sprinkle on breakfast cereals. Aspartame (Canderel brand sweetener), which many find more palatable, has a limited use because sweetening power is lost when it is subjected to prolonged heating. Patients with diabetes are prone to dyslipidaemia so attention to dietary fat intake is as important as good metabolic control. Protein Children with diabetes should have protein intakes no higher than those taken by other children. In the diets of most children protein provides 15% of dietary energy, although actual requirements are considerably lower than this [12]. The carbohydrate or energy allowance and distribution can then be tailored to the home situation and most appropriate insulin regimen. Providing the child is not overweight, the usual energy intake prior to the onset of diabetic symptoms can be used as a basis for deciding the diet. Regimens include: Low sugar and diabetic products Low calorie drinks are extremely valuable in the diet of a child with diabetes. Other low sugar products marketed for the general population can also be useful, for instance reduced sugar jams, fruit canned in natural juice, low sugar desserts. Diabetic products, however, have no place in the diet for the child with diabetes. Many families prefer using rapid acting analogue insulin in conjunction with long acting analogue insulin. There is no requirement to wait 30 minutes between injecting and eating because of the fast onset of analogue action, and most children appreciate this. The additional advantage of insulin analogue is that, because of its short period of action, snacks between meals are not always necessary. This is useful for teenagers trying to lose weight (especially girls) and those who find eating snacks tedious. Children who prefer to eat snacks (especially at bedtime) may prefer soluble insulin to cover the meal and snack rather than have an additional injection. Carbohydrate counting is increasingly more common amongst those on a basal bolus regimen. The family learn about the relationship of carbohydrate and insulin doses and therefore calculate the carbohydrate: insulin ratio. For example, if 4 units of insulin are given before a 40 g carbohydrate lunch and the resulting blood glucose level is satisfactory the family can assume that the child needs 1 unit of insulin per 10 g of carbohydrate. However, they must be prepared to use trial and error and to interpret the blood glucose results. Twice daily insulin It is important for children to take carbohydrate at regular intervals so that hypoglycaemia may be avoided and hyperglycaemia prevented. Meals should be consumed 30 minutes after an insulin injection of mixed soluble and isophane insulin (unless low blood sugar dictates otherwise) in order to optimise postprandial blood sugar profiles. A meal pattern of three meals and three snacks each day is appropriate for most children, although very young children and adolescents may need more snacks. Carbohydrate should be distributed throughout the day taking account of the peak periods of insulin action. The children are given around half of their required daily insulin as a total basal dose over the 24-hour period and the remainder is given as bolus doses before each meal and snack. The amount of insulin given as the bolus is dependent on the amount of carbohydrate consumed and the carbohydrate: insulin ratio. Split evening insulin the above applies, except that giving a dose of analogue or soluble insulin before the evening meal allows more flexibility. If more or less carbohydrate than usual is desired the insulin dose can be adjusted accordingly. The timing of the evening meal may also be adjusted, the soluble insulin 168 Clinical Paediatric Dietetics Table 10. The information should be delivered at a rate that considers the social, intellectual and cultural background of the child. Verbal instructions should be reinforced with appropriate written information and other resources should be used where possible. Whether quantitative or qualitative methods should be adopted continues to be a controversial subject. Limited evidence is available concerning the optimal type of diet therapy [16] and there is a lack of evidence to recommend either a qualitative or quantitative approach as the most effective. Most dietitians (88%) who provide a service to children with diabetes use quantitative methods [17]. At present the 10 g carbohydrate system (using handy measures) offers the best system for children, where a daily allowance of carbohydrate is given along with a suggested distribution at each meal and snack time for those on twice daily or split evening regimens. Children on basal bolus or pump therapy can use their knowledge of food and carbohydrate: insulin ratio to establish how much insulin to take for each meal and snack. Qualitative diet Alternative methods of dietary advice which do not Diabetes Mellitus 169 (a) 0 2 4 6 8 10 12 14 16 18 20 22 24 Rapid acting analogue Regular insulin Isophane insulin 30/70 insulin mix Slow acting analogue (b) 0 2 4 6 8 10 12 14 Time of day (h) 16 18 20 22 24 0 (c) 2 4 6 8 10 12 14 Time of day (h) 16 18 20 22 24 Figure 10. Bread Wholemeal or white Rolls, baps Breakfast cereals All Bran, Branflakes Cornflakes Weetabix Porridge Rice and pasta Brown or white rice cooked Spaghetti Pasta. This method is widely used in the treatment of adult diabetes but there is controversy over its use in childhood, particularly for very young children who may be erratic eaters and who may not accept or tolerate a high fibre diet [18]. A compromise may be to teach a measured diet initially on diagnosis, as many parents feel more secure using the 10 g exchange system, then to move onto an unmeasured diet when appropriate. Encouraging results have lead to the project being extended to children and young people. Hypoglycaemia Causes of hypoglycaemia include: l l l l l Exercise, without additional food or reduction in insulin dose Insufficient carbohydrate eaten, or being late for or missing a meal or snack Too much insulin or dose given at the wrong time Food not absorbed. The exact amount of carbohydrate is less important than the Symptoms are similar to those seen in the adult and mild hypoglycaemia symptoms include pallor, mood swings, irritability, headache, hunger and fatigue. If the hypoglycaemia is moderate, the child may be unaware of it, but may appear confused and unco-operative. Regular hypoglycaemic episodes indicate that the diet and insulin are out of balance and that the whole regimen needs assessing. The possibility of surreptitious extra insulin administration should also be considered. Examples include three glucose tablets, 50 mL glucose drink such as Lucozade, or two teaspoons of ordinary jam, honey or syrup. The suggestion of performing additional blood sugar testing at the time of a suspected hypoglycaemia is often enough to act as a deterrent. If hypoglycaemia occurs just prior to a meal, then sufficient quick acting carbohydrate should be given to alleviate symptoms and the meal or snack given soon after. If the next food is not due for an hour or more it is important to use a back-up of slower acting carbohydrate such as a digestive biscuit or piece of fruit in order to prevent blood levels dropping before the next meal. Moderate hypoglycaemia At the stage of moderate hypoglycaemia, the child will need help to take a sugary drink or food and Glucogel (formerly known as Hypostop) can be most useful. Glucogel, which is available on prescription, is a rapidly absorbed glucose gel in a tube packaging, which can be squeezed into the mouth if the child is unco-operative. This should be followed up with starchy carbohydrate once the child has recovered. Severe hypoglycaemia Most centres advise that parents keep an emergency supply of a GlucaGen HypoKit for severe hypoglycaemia. This is a glucagon injection to use at home if the child is unconscious or having seizures or if they are unable to resolve hypoglycaemic symptoms. Advice must be given on prevention of hypoglycaemia during and after additional activity. Exercise has the effect of lowering blood glucose levels by increasing the non-insulin dependent uptake of glucose by cells and increasing insulin sensitivity.

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Frequently in the production of ales with rapid top fermentation the temperature is allowed to rise unrestricted over the first 48 to 60 hours of fermentation erectile dysfunction treatment natural way generic 160mg malegra fxt plus with visa. An equation has been derived to calculate the amount of cooling required which can be applied to any fermentation situation (Anderson erectile dysfunction drugs at walgreens buy cheap malegra fxt plus 160 mg, et al erectile dysfunction statistics us order malegra fxt plus 160mg. This requires more cooling equipment with a consequent increase in revenue and capital cost impotence cure generic 160mg malegra fxt plus otc. However many vessels in use throughout the world are incapable of cooling at even half of this rate erectile dysfunction oil purchase 160 mg malegra fxt plus otc. Fermenters for lager fermentation are thus the most common and important in brewing and must allow for this property of the yeast erectile dysfunction doctor nashville generic malegra fxt plus 160mg on line. Nathan claimed faster fermentation rates and the collection of carbon dioxide as well as fermentation control by temperature and the use of the vessels for fermentation and maturation (Nathan impotence in young males purchase malegra fxt plus 160mg free shipping, 1930) erectile dysfunction blood flow discount malegra fxt plus 160mg otc. Before Nathan vessels were fully accepted some cylindrical tanks were built with gently sloping bases but these tanks were seldom fully successful for yeast removal. An important characteristic of these vessels is the steep angled cone at the base. This allows most of the yeast to be separated, leaving the beer comparatively free of yeast. This has allowed, in some systems, maturation and conditioning to take place in the same vessel as fermentation without the need to centrifuge the beer during transfer to a second vessel for maturation (Chapter 15). Heterogeneous fermentations have been observed in tanks much greater than 20 m (66 ft. This phenomenon has not been fully explained but special circumstances do apply to very large vessels (b 2,500 hl 1,500 imp. In classic European lager production more squat vessels are used where the ratio of diameter to height is ` 2:1. This gives a fermentation profile that equates more completely to that achieved in horizontal tanks. In tall vessels when the ratio is b 3:1, there is a tendency for increased production of higher alcohols at the expense of esters. This may be caused by increased amino acid utilization caused by the increased beer circulation generated by rapid carbon dioxide production. Doubling the size of the vessel leads to a cost increase of about 35% (Maule, 1977). In general the greater the volume to surface area ratio the lower the unit 516 Brewing: science and practice volume cost will be. A large volume of foam is formed by the evolution of carbon dioxide and this could cause pressure release valves to block. The headspace volume of the tank should therefore be at least 25% of the pitched wort volume. From this discussion it is difficult to generalize about the optimum size and aspect ratio of fermenters. As a general rule filling the vessel should not take longer than 12 hours, irrespective of the number of brews being run to the vessel for fermentation. Continuous filling with fresh wort will lead to increased production of -acetolactate and result in enhanced maturation time for diacetyl removal (Chapter 15). Mild steel was also prone to rusting and modern vessels are almost always constructed of chrome-nickel stainless steels. These steels are often referred to in brewing by the general classification V2A and V4A, but these categories cover a series of different alloys. Resistant properties of 316 steels are enhanced by the inclusion of molybdenum (Table 14. This is not usually a problem for fermenters but with liquors having high chloride contents 316 can be specified, but it is much more expensive than 304 steel. A very important factor is the surface smoothness of the steel that can be achieved in manufacture. It should be as smooth as is possible so that indentations cannot provide areas for potential microbial contamination. Cooling jackets the fermenter must be equipped with a cooling system to remove heat generated during fermentation and to allow the control of temperature to the required profile. In direct cooling ammonia gas is used as the refrigerant and cooling is achieved by expansion and evaporation of the liquefied gas. This coolant is circulated through the fermenting vessels and thence returned to the plant. Cooling jackets are constructed so that good heat exchange is possible and several designs are available. Limpet coils are wound onto the vessel surface and seam welded, they have a relatively heavy construction. This system has a low volume and is favoured with direct expansion cooling using ammonia. If properly specified and manufactured the design of the cooling jacket has little impact on fermentation performance. A fully equipped fermenter will probably have two cooling sections on the cylinder of the tank and a further section on the cone. Vessel fittings Vessels are filled and emptied from below, reducing oxygen ingress. Vessels are fitted with pipes for the addition of wort, the removal of yeast, and the removal of beer. There are also pressure relief and vacuum relief systems, which are fitted into a top-plate assembly. One of the main factors in the operation of these vessels is ensuring the integrity of the pipe-work systems so that yeast, wort, beer and cleaning fluids are, when required, handled separately and not allowed to mix. The different lengths of the Ushaped connection pipes make wrong connections impossible. The pathways so made are opened and closed by manual or remotely operated butterfly valves. The problem in this system is valve leakage which can cause severe damage if, say, cleaning fluid leaks into the beer. This assembly contains an upper and lower valve controlled by springs and separated by a small space. Opening the valve is 518 Brewing: science and practice achieved by compressed air, which overcomes the pressure of the springs. On release the compressed air escapes and the pressure of the springs takes over, this forces first the upper and then the lower valve to close. The small space between the valves still exists and if a valve is not properly sealed liquid will flow through the space and out of the assembly through a pipe. These systems are now favoured with the desire to lower manpower costs in breweries, but are only of use if closely examined frequently! Carbon dioxide produced during fermentation must be removed from the vessel irrespective of whether this gas is collected for further use (Section 15. This gas pressure must, therefore, be released and the vessel must also be protected against the development of a vacuum. For ease of manufacture and ease of operation it is now common practice to incorporate these fittings into a top plate of about 1 m (3 ft. If the vessels are standing in the open air this top plate must be protected against the weather. A reduction in pressure can occur on emptying the vessel, from the reaction of carbon dioxide with caustic detergents and when cold liquid enters the tank after hot cleaning. Vacuum relief valves incorporated into the top plate are often weight operated, working in the reverse mode to the pressure relief valve. Vessels will have a high organic soil level and will be best cleaned by a combination of liquid impact and detergent action. Many types of spray head are available but the most effective utilize (a) Weight moved to achieve required relief setting Guide pins Weight moved to achieve required relief setting (b) Guide pins. Outside tanks are insulated against ambient conditions, which obviously vary considerably throughout the world. Indoor tanks will also require some insulation to lessen the demands on the temperature control system. Insulation is best added to the tank during manufacture for vessels up to a size of around 2000 hl (1200 imp. Insulation materials usually contain chloride ions and so a chloride inhibiting layer must be applied to the tank to protect the stainless steel prior to the application of the insulation. There is a wide range of insulation materials available and individual companies often have very distinct preferences. Phenolic foam is less flammable although polyurethane can incorporate fire retardants, but these contain chloride. Inorganic materials such as glass fibre or mineral wool are completely non-flammable but are less good insulators. The capital cost of additional insulation is small in relation to the total cost of the vessel and so it is foolish to compromise here. This can be achieved with an aluminium foil applied over the insulation, which must be applied with care to avoid any points of potential water entry. Finally, the outdoor vessels must be externally clad to protect the insulation from weather and mechanical attrition. Jointing these sheets is critical so that water runs off the cladding and does not collect on the joint and hence gain access to the insulation. In hot countries, with high solar radiation and reflection light colours are best. Addition of yeast (pitching) the metabolism of wort by yeast is discussed in Chapter 12. Here we are concerned with the technical requirements for consistent fermentations. Only if the fermentation of wort can be performed reproducibly can the integrity of the beer brand be maintained. At the start of fermentation rapid yeast growth must be encouraged and this requires both the introduction of oxygen to the wort and very efficient mixing of the yeast with the wort. Clumping of yeast must be avoided so that the yeast cells can gain speedy access to the wort nutrients. In modern plant this intimate mixing is achieved by dosing yeast into a flowing stream of wort. This is essential for closed fermenters as it is impossible to pour yeast into the wort, as is the practice in some systems of open fermentation (Section 14. Using air a wort oxygen level of 8 to 9 mg/l is achievable and this is adequate for many 520 Brewing: science and practice fermentations. Over oxygenation is sometimes thought to be impossible because oxygen is so rapidly utilized by the yeast. However, with some strains of yeast excess oxygen in the wort can lead to overgrowth and lower ethanol yields. It is therefore good practice to match the oxygen requirement of each particular yeast strain (Chapter 13). Sintered ceramic candles can cause the injection of a very fine stream of bubbles to achieve intimate mixing but these systems are difficult to clean. Air or oxygen is introduced just before the constriction in the pipe and then mixes thoroughly with the wort in the turbulent flow resulting from the subsequent increase in diameter of the pipe (see also Chapter 10). The essence of successful pitching is the measurement of the quantity of the yeast to be pitched into the wort (Chapter 13). This can be achieved by volume, mass, or weight but these methods rely on the slurry being of constant composition and do not compensate for yeast viability. These methods are simple, cheap and can be successfully carried out by relatively unskilled personnel. A calibrated vessel can be used to measure the volume or more effectively a volumetric flow meter such as a magnetic flow meter. Account must be taken of the viability and concentration of the yeast to achieve good results. This cannot be assessed and hence markedly different carbon dioxide concentrations in different slurries will affect the amount of yeast pitched into the wort. The problem of trapped carbon dioxide can be avoided by the use of a mass meter. Again account must be taken of the viability and concentration of yeast in the slurry. Methods of this type are gaining use in breweries often in conjunction with instrumental systems to measure yeast concentration. If used with yeast slurries the weight method requires the yeast storage vessels to be installed on load cells so the vessel contents can be weighed. The method is also commonly used with pressed yeast cake, which is subsequently slurried in chilled water prior to addition. The main problem with these methods is the reliability of the load cells that do not work well in the conditions of the yeast storage area (wet and cold! As with other methods account must be taken of viability and concentration of the yeast. As simply applied these methods suffer from the inherent variability of yeast slurries in terms of viability and concentration. The number of cells in a yeast slurry can be estimated in a laboratory using a Coulter counter. This figure can then be used to estimate the volume of slurry needed to give a particular yeast count in the wort. To do this many brewers will apply a compensation factor to the amount of slurry to be pitched. In this method dead cells stain blue and viable cells remain colourless (Chapter 13). The method has, however, been considered unreliable for viabilities of ` 85% (Institute of Brewing, Analysis Committee, 1971). There have been recent attempts to improve methods of determining concentration and viability of slurries by using new technologies. There has also been the attempt to link 14 Fermentation technologies 521 these methods into automatic systems of yeast pitching in breweries to avoid laboratory involvement and devolve the control of the process to brewery personnel. The objective here has been to improve the consistency of brewery fermentations and achieve more predictable attenuation and flavour volatile production. A skid-mounted instrument has been described (Teass, 2000) that will provide instantaneous cell counts in the 0 to 2 billion cells/ml range. Results obtained with the instrument correlated well with laboratory measurements. The volume to be pitched is controlled by a flow meter but corrections for viability still have to be made. A biomass sensor measures the dielectrical permittivity of yeast cell suspensions. This system utilizes a radio-frequency signal to create an electrical field through which the yeast cell suspension can flow. The yeast slurry acts as a dielectric in that the electric field gives rise to no net flow of electric charge but only to a displacement of that charge. A reading of the displacement angle can be correlated with the concentration of intact cells. On-line and off-line instruments have been developed using this principle (Carvell et al. The sensor can be calibrated to different yeast strains used for different brewery fermentations. The actual pitching rate used varies considerably between breweries and rates of 5 to 20 million cells/ml of wort are common depending on the specific gravity of the wort. An optimum level is considered to be 10 to 12 million cells/ml and this should result in a reproduction rate for lager yeast of 3 to 5 times (Stewart and Russell, 1998). Temperature control the heat output during fermentation has been discussed (Section 14. It follows that for reproducible lager fermentation in a brewery this excess heat must be removed by the cooling system so that the temperature of the fermenting wort can be controlled to a chosen profile.

Thus top erectile dysfunction pills purchase 160mg malegra fxt plus free shipping, if throughput rates are too high the continuous addition of glucose in fresh wort can repress maltose utilization erectile dysfunction forum order malegra fxt plus 160mg overnight delivery. This problem can be circumvented by the use of continuous systems containing two or more discrete stages erectile dysfunction email newsletter buy cheap malegra fxt plus 160 mg on-line. In the absence of a complete growth medium erectile dysfunction treatment perth buy generic malegra fxt plus 160mg on-line, glucose-starved cells exposed to glucose exhibit a transient repression response erectile dysfunction ka desi ilaj buy 160 mg malegra fxt plus with visa. Following addition of the limiting nutrient condom causes erectile dysfunction malegra fxt plus 160mg discount, a source of nitrogen for example impotence trials purchase malegra fxt plus 160 mg without a prescription, the typical glucose repression response is seen erectile dysfunction drugs herbal purchase malegra fxt plus 160 mg free shipping. It has been suggested that yeasts require additional controls that prevent the full-blown glucose repression response in the absence of a complete growth medium. This signalling mechanism is described as the fermentable-growth-medium induced pathway (Thevelein and Hohmann, 1995). The Pasteur effect is the phenomenon whereby fermentation is inhibited by respiration or glycolytic rates decrease under aerobic conditions (Warburg, 1926). The energetic yield of respiration is more favourable than fermentation and furthermore, yields of cellular biomass per unit of sugar consumed are greater. It would be supposed, therefore, that under aerobic conditions yeast would preferentially use oxidative phosphorylation for the generation of energy and in consequence reduce rates of glycolysis. The magnitude of the Pasteur effect is dependent on the relative respiratory capacities of individual yeast strains. In the former yeast, a comparatively small Pasteur effect is observed only in glucose or nitrogen-starved stationary phase cultures. The mechanism of the Pasteur effect is obscure and possibly differs depending on cultural conditions and the nature of the yeast. In derepressed cells undergoing a transition from anaerobiosis to aerobiosis the effect may be due to simple competition for pyruvate. Since pyruvate dehydrogenase has a higher affinity for pyruvate compared to pyruvate decarboxylase the presence of oxygen allows carbon to be diverted towards respiratory pathways and fermentation rates decline. Decrease in glycolytic rates by aerobiosis appears to involve feed-back control from oxidative phosphorylation. The mechanism is unknown although it has been suggested that glycolytic rates might be modulated by the effect of phosphate on the activity of phosphofructokinase (Gancedo and Serrano, 1989). The proposal is that under anaerobic conditions, flux through oxidative phosphorylation is reduced and this results in an increase in phosphate concentration. In turn, this activates phosphofructokinase and glycolytic activities are stimulated. Other mechanisms regulating sugar metabolism in various genera of nonbrewing yeasts have been discovered, for example the Custers and Kluyver effects. With regard to commercial fermentations, in which ethanol is 12 Metabolism of wort by yeast 439 a major product of yeast metabolism, the rate of ethanol formation and the maximum concentration formed may be important considerations. In the case of the fermentation of high-gravity worts the ability of yeast to withstand high concentrations of ethanol is an influential factor in strain selection. Exposure of yeast to very high ethanol concentrations results in the inhibition of growth and ultimately death. Some strains are more able than others to withstand the deleterious effects of ethanol. Of course, it is possible that intermediates of ethanol formation or other products of fermentation exert deleterious effects on yeast. In addition, in order to generate high ethanol concentrations during fermentation, it is necessary to provide a high initial concentration of fermentable sugar. In this case, the ability to grow under conditions of low water activity may be of greater or equal importance to ethanol tolerance, per se. In order to ferment concentrated worts it is essential that other nutrients are available in balanced quantities. This is an important consideration in high-gravity brewing where the injudicious use of sugar adjuncts may result in wort that is deficient in non-sugar nutrients. Many reports describe morphological changes in response to ethanol exposure, for example, the development of cell surface invaginations and cell shrinkage (Pratt-Marshall et al. The toxic effects are apparently more severe when ethanol is generated endogenously compared to the same concentration added to the medium (Nagodawithana and Steinkraus, 1976). This observation prompted the suggestion that the effect was a consequence of intracellular accumulation of ethanol during fermentation. The severity of the inhibition is proportional to the chain-length of the molecule. Several mechanisms have been proposed by which the toxic effects of ethanol may be exerted. The major site for ethanol toxicity appears to be the plasma membrane and other intracellular membranes. These include leakage of cellular components, abolition of membrane proton motive potential, inhibition of transport systems and alterations in membrane structure and fluidity. The fact that the membrane is the primary target explains the observation that longer chain-length alcohols have enhanced toxicity. Thus, there is a concomitant increase in hydrophobicity and consequently easier interaction with membrane lipids. The observation that endogenously generated ethanol is more toxic than added ethanol at similar concentration suggests that other intermediates of ethanol biosynthesis might be influential. Potential candidates include short chain fatty acids, higher alcohols, acetate and in particular acetaldehyde (Jones, 1987). The argument is perhaps most 440 Brewing: science and practice persuasive in the case of acetaldehyde since reportedly, it is an order of magnitude more toxic to yeast than ethanol and is the immediate precursor of ethanol (Jones, 1989). However, the fact that acetaldehyde can accumulate in yeast cells, under some conditions, to a greater concentration than seen in fermentation and apparently with no toxic effect provides a powerful counter-argument (Stanley and Pament, 1993). It is perhaps most likely that intermediates of ethanol metabolism may contribute to ethanol toxicity in a synergistic fashion. Ethanol elicits a stress response such that there is a concomitant acquisition of thermotolerance and barotolerance (Hisada et al. In addition, there is an increase in levels of intracellular trehalose (Mansure et al. The lipid composition of membranes is altered such that there is an increase in the content of unsaturated fatty acids and 5,7unsaturated sterols and a decrease in saturated lipids. Of course, this response is not possible in a brewing fermentation where these syntheses are precluded by anaerobiosis. The toxic effects of ethanol are reportedly ameliorated by the presence of Mn-superoxide dismutase, the mitochondrial enzyme implicated in resistance to oxidative stress Costa et al. Therefore, it would not be active under the conditions of a brewing fermentation (Section 12. The tolerance of yeast to ethanol can be influenced by manipulation of the growth medium. Predictably, supplementation of the medium with a source of unsaturated fatty acids is beneficial in this regard. A considerable body of evidence has now been amassed indicating that the addition to growth media of various metal ions provides protection against ethanol stress. In particular, calcium and magnesium have been reported to have beneficial effects (Dombek and Ingram, 1986; Ciessarova et al. It has been suggested that wort may not contain optimal concentrations of these metal ions (Walker et al. This can be remedied by supplementation with magnesium to ensure that the ratio of this metal ion to calcium is always high. Facultative anaerobic strains such as brewing yeasts have the ability to grow either oxidatively or fermentatively. The effects of glucose catabolite repression in Crabtree positive yeast are relieved in the absence of a glucose signal. However, development of complete respiratory competence requires the presence of oxygen. Thus, aerobiosis provides yeast with the opportunity of utilizing the energetically favourable oxidative route for energy production. However, oxidative metabolism is accompanied by the generation of potentially harmful reactive oxygen radicals. Consequently, yeast must have enzyme systems for removal of oxygen radicals and nullifying this potential threat. The role of many of these is unknown, however, some are involved in the assimilation of nutrients from the medium which otherwise require oxygen for their synthesis. Hypoxic genes are expressed strongly under micro-aerophilic conditions and are apparently required for the efficient utilization of low oxygen concentrations. The expression of more than 200 genes is required for aerobic respiratory growth (Tzagoloff and Dieckmann, 12 Metabolism of wort by yeast 441 1990). These include components of the electron transport chain such as ubiquinone and cytochrome oxidase. The signal pathway by which molecular oxygen exerts its effects upon metabolism is unknown. However, as described in the previous section in the hierarchy of signalling pathways, it plays a subordinate role to glucose repression. Consequently, haem content and oxygen tension are directly related (De Winde and Grivell, 1993). In addition to its role as a prosthetic group in molecules such as cytochromes, haem is an effector metabolite in many pathways that utilise molecular oxygen. It is involved in the positive regulation of expression of genes encoding respiratory enzymes and those that play a part in protecting the cell against oxygen radicals. Conversely, haem represses the expression of several genes that are redundant under anaerobic conditions. These include some of those responsible for the synthesis of sterols and unsaturated fatty acids. Brewing yeasts do not develop respiratory competence under the conditions encountered in fermentation. Thus, in the aerobic phase of fermentation, respiratory pathways are repressed because of the presence of sugars. In late fermentation when the sugars have disappeared and their repressing effects are relieved, anaerobiosis prevents the induction of the respiratory enzymes. In a study of type species from 75 genera, it was noted that only 23% could grow under anaerobic conditions on a complex medium supplemented with ergosterol and a source of unsaturated fatty acids (Visser et al. These essential metabolites can be assimilated from the medium or synthesized de novo from carbohydrates. In brewery fermentations, sterols and unsaturated fatty acids are synthesized during the aerobic phase. Cell proliferation during the anaerobic phase of fermentation dilutes the pre-formed pools of sterols and unsaturated fatty acids amongst daughter cells. On subsequent re-pitching, these lipids must be replenished hence the requirement for oxygenation of wort. Failure to provide sufficient oxygen is one of the prime causes of slow and sticking fermentations. In an early study, ale strains were classified as requiring half air saturation, air saturation, oxygen saturation or more than oxygen saturation for satisfactory fermentation performance (Kirsop, 1974). Similar findings have been reported for lager yeast strains (Jacobsen and Thorne, 1980). The explanation for these differences is related to the spectrum of sterols produced by individual yeast strains (Section 12. The fate of most of the oxygen utilized during the aerobic phase of fermentation is unknown. Theoretically 10% is utilized for sterol formation and 15% for the biosynthesis of unsaturated fatty acids (Kirsop, 1982). Many essential energy-requiring enzyme systems are located within promitochondria, the undifferentiated organelles characteristic of fermentative yeast. Oxygen radicals are highly reactive species, which are implicated in damaging effects such as lipid peroxidation, mutagenesis and other degenerative changes associated with ageing and senescence. Yeast, in common with other cells, possesses protective mechanisms for removing oxygen radicals (Krems et al. The precursor of sterols, squalene, reportedly scavenges free radicals in mammalian cells (Kohno et al. Similarly, reduced glutathione reacts with superoxide, hydrogen peroxide and larger hydroperoxides. These enzymes, acting in concert, convert the superoxide radical to oxygen and water. In addition, it is induced in response to stresses such as heat shock, low water activity and oxidative stress (Dawes, 1999). These observations have resulted in the suggestion that catalase this involved in hydrogen peroxide removal during the stationary phase, whereas, catalase A is protective towards sudden oxidative stress. Frequently they form part of larger macromolecules where the hydrophobic nature of the lipid moiety confers specific properties. Many lipids have biological roles in signalling systems, as vitamins and in receptor sites on cell surfaces. The predominant classes of lipid are sterols (both free and 12 Metabolism of wort by yeast 443 Table 12. Fatty acids, either free or esterified as diacylglycerols and monoacylglycerols make up most of the remaining lipid (Table 12. The predominant saturated fatty acids are palmitic (16:0) and stearic (18:0) with smaller amounts of myristic (14:0) and lauric (12:0). Unsaturated fatty acids are mainly palmitoleic (16:1), oleic (18:1) and linoleic (18:2). Principally, it is derived from glucose catabolism from pyruvate, directly or via acetaldehyde, acetate and acetyl-CoA synthetase. It is formed from the catabolism of amino acids, leucine, lysine, tryptophan, tyrosine and phenylalanine. In addition, acetylCoA is the end-product of the -oxidation pathway for the degradation of fatty acids. The biosynthetic pathway to fatty acids involves the action of two enzyme systems, acetyl-CoA carboxylase and the fatty acid synthase complex. The additional carbon atom is derived from bicarbonate ion in a reaction involving the coenzyme biotin. Acetyl-CoA carboxylase is considered the rate-determining step in fatty acid biosynthesis. The two carbon atoms are donated by malonyl-CoA deriving from the activity of acetyl-CoA carboxylase. Multiple desaturation reactions result in the synthesis of di-and trienoic acids such as linoleic (18:2) and linolenic (18:3) acids. Fatty acids, both saturated and unsaturated, eventually become located in membranes where they have structural roles. The relative chain lengths and degrees of unsaturation are influenced by environmental conditions. For example, as the growth temperature is reduced there is a need to maintain membrane fluidity. This is achieved by increasing the degree of unsaturation of the fatty acids in membrane lipid components. The elongation reactions occur prior to insertion of fatty acids into membranes (Schweizer, 1999). Fatty acid biosynthesis occurs in the cytosol, although there is evidence that yeast may possess a second mitochondrial fatty acid synthase (Schneider et al. The first and rate limiting step in the pathway is catalysed by an acyl CoA oxidase and converts fatty acyl-CoA esters to trans 2, 3-dehydroacyl-CoA esters and hydrogen peroxide. In the next sequence of reactions, catalysed by a multifunctional enzyme, trans 2, 3-dehydroacyl-CoA esters are successively modified by the action of trans 2-enoyl CoA hydratase and 3-hydroxyacyl CoA dehydrogenase. Finally, 3-ketoacyl CoA thiolase releases a molecule of acetyl-CoA leaving a residual acyl-CoA chain two carbon atoms shorter than the original. The three enzymes of -oxidation are induced during growth on fatty acids under aerobic conditions. Fatty acids are transported from the cytosol into peroxisomes via transporters specific for medium chain length and long chain length fatty acids. The acetyl-CoA generated by oxidation is transported back into the cytosol via a carnitine/acetylcarnitine shuttle system or as citrate. In the latter case, the acetyl-CoA is acted upon by a peroxisomal citrate synthase. In view of the susceptibility to glucose repression and requirement for oxygen, oxidation is unlikely to play any part in brewery fermentations. The free 1, 2-hydroxyl groups of glycerol 3-phosphate are acylated by two 446 Brewing: science and practice molecules of fatty acyl-CoA to yield a phosphatidic acid. The resultant diacylglycerol reacts with a third molecule of fatty acyl-CoA ester to form a triacylglycerol. Two phosphatidic acid phosphatases occur, one microsomal and another that is located in mitochondria. In non-oleaginous yeasts, such as brewing strains, triacylglycerols are synthesized only when the fatty acid requirement for phospholipids is satisfied. The fatty acids may be mobilized by the action of lipases, providing an alternative source of fatty acids for phospholipids synthesis.