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Publisher Summary This chapter explores that gonorrhoea is one of the most commonly reported communicable diseases. With the appearance of antibiotic-resistant strains of Neisseria gonorrhoeae (N. gonorrhoeae), which are thought to be the result of an intergeneric conjugal transfer, the possible loss of efficacy of drug treatment in control of this disease has been forewarned. The development of a vaccine follows basic understanding of human immunity to gonococcal infection because gonorrhoea has no virulence factor against which the person could be easily immunized. The multifactorial nature of virulence and the mechanisms of pathogenesis are examined by an understanding of the basic biology of the gonococcus. This chapter provides a summary of the important aspects of gonococcal physiology that relate directly or indirectly to the disease process. Certain aspects of the physiology and metabolism may be as yet unrelated to pathogenesis, but they provide a base from which future research can be planned. It discusses the differences and similarities between the physiology of N. gonorrhoeae and other pathogenic and non-pathogenic Neisseria spp., where this information is available and pertinent. Knowledge of the physiology of related species may help to delineate subject areas of gonococcal physiology that require additional effort.

The metabolism of glucose was examined in several clinical isolates of Neisseria gonorrhoeae . Radiorespirometric studies revealed that growing cells metabolized glucose by a combination on the Entner-Doudoroff and pentose phosphate pathways. A portion of the glyceraldehyde-3-phosphate formed via the Entner-Doudoroff pathway was recycled by conversion to glucose-6-phosphate. Subsequent catabolism of this glucose-6-phosphate by either the Entner-Doudoroff or pentose phosphate pathways yielded CO 2 from the original C6 of glucose. Enzyme analyses confirmed the presence of all enzymes of the Entner-Doudoroff, pentose phosphate, and Embden-Meyerhof-Parnas pathways. There was always a high specific activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) relative to that of 6-phosphogluconate dehydrogenase (EC 1.1.1.44). The glucose-6-phosphate dehydrogenase utilized either nicotinamide adenine dinucleotide phosphate or nicotinamide adenine dinucleotide as electron acceptor. Acetate was the only detectable nongaseous end product of glucose metabolism. Following the disappearance of glucose, acetate was metabolized by the tricarboxylic acid cycle as evidenced by the preferential oxidation of [1- 14 C]acetate over that of [2- 14 C]acetate. When an aerobically grown log-phase culture was subjected to anaerobic conditions, lactate and acetate were formed from glucose. Radiorespirometric studies showed that under these conditions, glucose was dissimilated entirely by the Entner-Doudoroff pathway. Further studies determined that this anaerobic dissimilation of glucose was not growth dependent.

Cathepsin G, a cationic serine esterase derived from the azurophilic granules of human PMNs, exerts potent anti-gonococcal activity in vitro. Cathepsin G is likely to contribute to the ability of PMNs to kill ingested gonococci by oxygen-independent means. We have found that cathepsin G has the capacity to cleave certain gonococcal proteins, predominate among these proteins is outer membrane protein PHI. We have also determined that a certain mutation which influences lipopolysaccharide structure increases the exposure of PHI resulting in increased susceptibility of gonococci to the bactericidal capacity of cathepsin G. Although bactericidal activity is independent of serine esterase activity, our data implicates PIII as a surface-exposed target for binding cathepsin G.

Neisseria gonorrhoeae strains with plasmid-mediated, high-level tetracycline resistance (TRNG) have accounted for approximately 5% of gonococcal isolates in patients attending the DeKalb County Health Department Sexually Transmitted Diseases clinic in Atlanta, GA, in August-December, 1985.

SummaryGlucose-limited cultures of N. gonorrhoeae were susceptible to autolysis. The onset of autolysis was not due to a decrease in pH but rather from depletion of the energy source. Cultures limited by nitrogen or by the addition of chloramphenicol or rifampicin were not susceptible to autolysis. The prevalence of autolytic strains appears to be wide spread.

Strains of Neisseria gonorrhoeae exhibiting high-level tetracycline resistance (TRNG) due to a 25.2-Mdal conjugative-tetM plasmid have been isolated in the United States. Ninety-nine TRNG isolates were characterized by auxotype and serovar (A/S class), plasmid content, and antimicrobial susceptibility patterns. TRNG isolates belonged to 19 A/S classes. Pro/IB-1 TRNG isolates accounted for 53 (53.5%) of 99 TRNG isolates, and were associated with a microepidemic of gonorrhea in homosexual men in Oregon. TRNG accounted for 4% of gonococcal isolates in DeKalb County, GA, in September-December, 1985, and continue to be isolated in this community. With the exception of 3 PPNG/TRNG isolates, TRNG isolates were susceptible or moderately resistant to other antimicrobial agents. TRNG have been isolated from 17 states in the United States and in British Columbia, Canada.

The effects of progesterone on the growth of pathogenic and nonpathogenic species of Neisseria were studied in liquid cultures. Only strains of N. gonorrhoeae and N. meningitidis were highly sensitive to growth inhibition by progesterone. This inhibitory effect was either bacteriostatic or bactericidal, depending upon the ratio of progesterone concentration to cell mass. The site of progesterone inhibition appeared to be located in the cell membrane; >86% of [4- 14 C]progesterone was recovered in the lipid-containing cell fractions. Membrane preparations from N. gonorrhoeae bound progesterone more efficiently than those from progesterone-insensitive cells. In addition, progesterone significantly inhibited the activity of the membrane-associated enzymes reduced nicotinamide adenine dinucleotide oxidase and (cytochrome b ) l -lactate dehydrogenase.

The diminished capacity doctrine allows a mentally abnormal but legally sane defendant to have his or her mental abnormality taken into account in assessing criminal liability.’ Depending on the jurisdiction, diminished capacity operates either to negate an element of the crime charged, thereby exonerating the defendant of that charge, or formally to reduce the degree of crime for which the defendant may be convicted and punished even if all the formal elements of the originally charged offense were satisfied. These two variants of diminished capacity will be referred to respectively as the “mens rea” and “partial responsibility” approaches.’ This contribution will analyze the theoretical basis and development of diminished capacity doctrine with special reference to the law in the State of California, where the doctrine is especially fully, if not coherently, developed. I shall contend that although the doctrine appears to express intuitively held notions about moral and legal responsibility, it is neither morally necessary nor socially desirable. In the alternative, it will be claimed that if moral intuitions

Gonorrhea has been known since antiquity. Today, this disease is the most commonly reported infectious disease in the U.S. The natural environment of the etiological agent, Neisseria gonorrhoeae, is man. In this host, the organism usually parasitizes mucosal surfaces populated by columnar epithelial cells. Under certain conditions, the gonococcus may disseminate or spread to adjacent organs. The gonococcus is well adapted to its environment and is a successful parasite. Until recently, gonococci were uniformly sensitive to penicilin. However, a plasmid encoding beta-lactamase has been identified in some isolates. Most strains exhibit specific requirements for various amino acids, vitamins, purines, and pyrimidines. Only glucose, pyruvate, and lactate are utilized as sources of energy. Glucose is dissimilated by a combination of the Entner-Doudoroff and pentose phosphate pathways. A tricarboxylic acid cycle is also present and active under certain conditions. Structurally, the cell envelope of the gonococcus resembles that of a typical Gram-negative bacterium. Gonococci are highly autolytic, especially in older cultures or after depletion of the energy source. Autolysis is not due solely to peptidoglycan hydrolysis, but appears to involve a destabilization of the outer membrane as well. Cell surface components such as pili, lipopolysaccharide, outer membrane proteins, and a capsule are associated with the virulence and pathogenicity of this organism.

This report concerns the interaction of gonadal steroids with Neisseria gonorrhoeae. Growth of gonococci in nutrient broth was inhibited by testosterone propionate at 20 and 40 μg/ml,and by testosterone and 19-nortestosterone at 40 μg/ml. Progesterone was more effective than the three androgens; concentrations as low as 1 μg/ml significantly inhibited growth. A specific relationship of the degree of growth inhibition to the quantity of organisms present was apparent. In addition, progesterone influenced gonococcal virulence. Inoculation of chick embryos with untreated organisms produced a 73% mortality, whereas inoculation of hormonally treated organisms produced a 34% mortality. Progesterone appeared to retard optimal cell functioning. Studies on the viability of gonococci in nutrient broth indicated a steroidal enhancement of survival. In control suspensions, viable organisms were detected for 15 days: in suspensions containing progesterone at 10 μg/ml. viable gonococci were detected for 25 days. Hormonally treated bacteria that had remained viable for 22 days retained virulence for chick embryos. The data are discussed in terms of possible modification of gonococcal pathogenesis.

Publisher Summary This chapter describes the assays for determining macrophage intrinsic antiviral activity and assessing extrinsic antiviral activity by measuring the ability of the macrophage to reduce virus growth in infected susceptible host cells in mixed culture. Virus titers are calculated from the plaque counts and dilutions. The virus titer sof macrophages lower than corresponding thermal inactivation controls suggest virus clearance from the macrophage or prolonged eclipse phase of virus in the macrophage. Slope of curve can be used to determine the rate of clearance. The number of plaques gives the number of infectious centers, that is, the number of macrophages containing infectious or potentially infectious virus. Extrinsic antiviral activity, the ability of certain mononuclear phagocytes to reduce virus growth in infected susceptible host cells on mixed culture, is another means by which macrophages may assist in host defense against viruses.

Publisher Summary This chapter discusses the biologically active components and properties of Bordetella pertussis. A variety of biological effects are observed in experimental animals following injection of phase I Bordetella pertussis cells or products. It includes sensitization to the lethal effects of the pharmacological agents histamine and serotonin as well as to nonspecific stresses such as cold and peptone shock; unresponsiveness to the induction of hyperglycemia by epinephrine, which has been attributed to the causation of a β-adrenergic blockade; leukocytosis with predominating lymphocytosis; adjuvanticity with respect to both antibody production—including reaginic antibody ( IgE )—and cell-mediated immunity; and direct, acute toxic effects which are in general related to either a distinct heat-labile toxin or to heat-stable lipopolysaccharide endotoxin. In addition, components of B. pertussis can be shown to induce striking effects in in vitro systems. Paradoxically, while clinical pertussis has become of decreasing importance where effective vaccines are routinely used; there has been an increased interest in the biological activities of B. pertussis.

Gonococci and meningococci are obligate human pathogens that can infect diverse sites within the human host. Each of these sites represents a unique niche with respect to nutrients, environmental factors, and competing microorganisms. The growth environment has a marked effect on the metabolism and cellular composition of Neisseria gonorrhoeae and N. meningitidis. Altered cellular composition is often reflected by changes in the cell surface that can ultimately affect the interaction of these microorganisms with the human host. The physiology and metabolism of the pathogenic Neisseria spp. have not been reviewed since 1979 (41). This review will discuss selected areas that have implications for the pathogenesis of these important microorganisms.

Neisseria gonorrhoeae readily underwent autolysis when suspended in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer at alkaline pH values. Autolysis was inhibited by the addition of Mg2+ or other divalent cations. Autolysis was also suppressed at acid pH (pH 6.0). Suspension of cells in buffer was accompanied by the hydrolysis of peptidoglycan. The rate of peptidoglycan hydrolysis in HEPES buffer was maximal at pH 8.5 and was similar in the presence or absence of Mg2+. Therefore, divalent cation stabilization against autolysis is not mediated by inhibition of peptidoglycan hydrolysis. Peptidoglycan hydrolysis occurred in HEPES buffer (pH 6.0), but at a rate that was 50% of the maximum. Incubation of cells with chloramphenicol or rifampin before suspension in HEPES buffer (pH 8.5) partially prevented autolysis; under these conditions, peptidoglycan hydrolysis still occurred, but at a reduced rate. Old and new peptidoglycans were hydrolyzed at similar rates. Peptidoglycan hydrolysis results in solubilization of both the peptide and glycan moieties.

The addition of 10 microgram of penicillin G per ml to log-phase cultures of Neisseria gonorrhoeae JW-31 (minimum inhibitory concentration for penicillin G, less than 0.007 microgram/ml) resulted in cellular lysis after a lag of 30 min. Penicillin markedly decreased the rate of peptidoglycan synthesis and enhanced the rate of hydrolysis of existing peptidoglycan. Hydrolysis was initiated immediately after addition of penicillin; cellular lysis did not occur until a considerable percentage of the peptidoglycan had been degraded. Cellular lysis was not due to penicillin per se but resulted from inhibition of cell wall synthesis. When cells were grown in media buffered with N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid at pH 6, penicillin did not cause lysis; however, at this pH, peptidoglycan hydrolysis occurred and cells lost viability at the same rate as in the control (pH 7.2). We suggest that the stability of gonococci grown at pH 6 is related to increased stability of the outer membrane. The penicillin-enhanced rate of peptidoglycan hydrolysis decreased approximately 50% at pH 6.0. Penicillin-enhanced lysis, peptidoglycan hydrolysis, and loss of viability were also markedly reduced in cells grown at 28 degrees C.

A variety of effects are produced in mice and rats following the injection of intact killed phase I Bordetella pertussis, extracts of the cells, or culture supernatant fluids. Among these effects are (1) Leucocytosis with a predominating lymphocytosis (Morse, 1965; Morse and Bray, 1969). (2) Increased sensitivity to the lethal properties of histamine, serotonin, acetylcholine, and bradykinin as well as increased sensitivity to nonspecific stimuli such as endotoxin and cold stress (reviewed by Munoz and Bergman, 1968). (3) Enhanced antibody formation (Dresser et al., 1970) including a greater production of homocytotropic antibody in response to a given antigen (Mota and Peixoto, 1966). (4) Heightened susceptibility to both active (Malkiel and Hargis, 1952) and passive systemic anaphylaxis (Munoz and Anacker, 1959). (5) Hypoglycemia (Stronk and Pittman, 1955) and a decreased hyperglycemic response to epinephrine (Fishel and Szentivanyi, 1963), effects that are presumed to be due to beta adrenergic blockade.

IN 1941 Kveim1 described a new skin reaction in which the intracutaneous injection of a homogenate of human sarcoidal tissue led to the formation of a nodule at the test site over the course of several weeks in patients with sarcoidosis, but not in normal subjects or persons with other diseases. Numerous investigators have subsequently studied this reaction, and most of them have supported the claim of its specificity for sarcoidosis.2 3 4 5 6 7 8 9 10 However, the dissenting opinion of one group of workers tended to cast some doubt on the validity of the Kveim test.11 , 12 This communication presents the results of a Cooperative . . .

SummaryThe majority of rabbits subjected to single intrapharyngeal infections with group A streptococci developed cardiac lesions characterized by muscle necrosis, cellular infiltration with mononuclear cells and Anitschkow myocytes and disruption of collagen. After multiple infections, fibrosis occurred and giant cells were also observed. Bacteria could not be demonstrated in any lesion. In 3 control groups, comparable lesions were absent in the hearts of all but one rabbit. The appearance of myocardial lesions within 24 hours of induction of pharyngeal infection suggests that a non-immunologic mechanism is involved.

Publisher Summary Current knowledge of the chemistry of cell-wall antigens of gram-positive bacteria, or the biologically and serologically important cell-wall antigens of gram-positive bacteria, is discussed in this chapter. In contrast to the soluble capsular antigens, especially those of pneumococci, the true cell-wall antigens have only relatively recently been available in under-graded form suitable for chemical and immunochemical analysis; and it is mainly the carbohydrate and teichoic acid rather than the protein components which have been studied. The cell walls provide the best source of immunizing antigens. Bacteria and their products can affect immune responses other than by acting as a source of antigenic materials . Despite certain basic similarities, there are sufficient differences between the cell walls of gram-positive and gram-negative organisms to warrant separate consideration. The cell wall of gram-positive organisms is clearly visible as a single layer distinct from the underlying cell membrane. Both protein and carbohydrate antigens have been found in the cell walls of gram-positive bacteria. Some of the antigens serve as serological determinants of group or type specificity; others such as streptococcal m protein also play important roles in microbial pathogenesis and virulence.. Intracellular, capsular, and diffusible antigens related to the cell wall of gram-positive bacteria, for example, the intracellular glycerol teichoic acids and capsular and diffusible antigens are related to the gram-positive bacteria.

The metabolism of glucose during enterotoxin B synthesis in Staphylococcus aureus S-6 was examined under anaerobic conditions in the presence and absence of nitrate. The repression of enterotoxin synthesis which occurs during the oxidative metabolism of glucose was relieved after a shift to anaerobic conditions; glucose was then converted primarily to lactic acid and was metabolized more rapidly, presumably to obtain the equivalent amount of energy available aerobically. A greater proportion of oxidized end products and evidently more energy per glucose molecule was produced in the presence of oxygen. Thus, available energy as judged by a change in the type and proportion of end products appears to be related to the degree of toxin repression. As expected, the addition of nitrate during anaerobic glucose metabolism prevented derepression of toxin synthesis.

Antibody to poliovirus type 1 (Po-1) was coupled to peroxidase by use of glutaraldehyde or 4, 4′ -difluoro,3, 3′ -dinitro diphenyl sulfone. Glutaraldehyde was found to be the superior coupling agent, yielding conjugates that had up to 2.8 × 10 4 enzyme units/ml (75% of total enzyme input). Conjugates migrated as a single band when centrifuged in sucrose density gradients, demonstrating that the purification procedure used was effective in removing both noncoupled enzyme and heterogeneous antibody components. Conjugates were specific for Po-1 and did not adsorb to cells infected with unrelated enterovirus types. Adsorption of conjugates to Po-1-infected cells was demonstrable within 6 h postinfection.

COAGULASE-negative strains of Staphylococcus albus added to suspensions of rabbit polymorphonuclear leucocytes in normal rabbit serum are rapidly phagocytosed and destroyed; in contrast, coagulase-positive strains of Staphylococcus aureus resist ingestion and survive extra-cellularly. The addition of anti-serum prepared against heat-killed S. aureus results in efficient phagocytosis and intracellular killing of the homologous organism1. The present communication describes the isolation and properties of a substance obtained from culture filtrates of an encapsulated S. aureus which interferes with its phagocytosis.

Chloroquine has been administered to seven patients with chronic sarcoidosis. In each instance there was considerable improvement of the cutaneous lesions. Regression of extracutaneous lesions was more variable, but improvement was often observed; this was particularly true of mucous membrane and thoracic node involvement. Associated with the clinical response, elevated sedimentation rates and high gamma globulin levels returned toward normal. It is suggested that chloroquine may be a useful drug for the treatment of many patients with sarcoidosis, and further studies are in progress to define the situations in which its use is of most benefit.

SEVERAL years ago the isolation of a surface antigen from culture supernatants of a mucoid strain of Staphylococcus aureus was reported1,2. The material, from strain Smith, was designated as SSA (Smith surface antigen). It consisted primarily of an amino sugar which did not behave as the usual 2-deoxy-2-amino-hexose, and which rapidly decomposed during acid hydrolysis. Later, the unknown substance was characterized as 2-deoxy-2-amino-glucuronic acid3.

During the transition between the exponential and stationary phases of growth, there was a rapid accumulation of both cell-associated and extracellular enterotoxin B. Extracellular enterotoxin was synthesized until the cells entered the stationary phase during which cell-bound toxin was not detected. The differential rate of toxin synthesis relative to that of total protein synthesis was greater at p H 7.7 than at 6.0. Addition of glucose decreased the differential rate of toxin synthesis. This decrease was greater at p H 7.7 than at 6.0. Addition of pyruvate decreased the differential rate at p H 7.7 but not at 6.0. Analysis of the nongaseous end products of glucose and pyruvate metabolism showed that conditions which favor the oxidative decarboxylation of pyruvate also favor the repression of toxin synthesis. Elimination of thiamine from the medium prevented the oxidative decarboxylation of pyruvate by Staphylococcus aureus S-6 and partially or completely reversed the repression of toxin synthesis by glucose and pyruvate. In the absence of an added energy source, thiamine starvation caused a decrease in protein synthesis but an increased differential rate of toxin synthesis which was greater at p H 7.7 than at 6.0. In the absence of thiamine, pyruvate was not metabolized but caused a decrease in the rate of protein synthesis. This resulted in a twofold increase in the differential rate of toxin synthesis. Thus, conditions which altered the oxidative decarboxylation of pyruvate or decreased the rate of protein synthesis increased the rate of enterotoxin B synthesis.

The mechanism by which Bordetella pertussis organisms and their products induce lymphocytosis in mice was analyzed in terms of the localization of syngeneic Cr-51-labeled lymph node cells. Labeled lymphoid cells incubated in vitro with the supernatant of B. pertussis cultures and then injected intravenously into normal recipients, or labeled cells injected into pertussis-treated recipients were unable to "home" to lymphoid organs but persisted for long periods in the blood. In animals "equipped" with a population of Cr-51-labeled lymphoid cells, administration of B. pertussis organisms or culture supernatant effected a shift of radioactivity from lymph nodes and spleen into the peripheral blood, coincident with the lymphocytosis. In in vitro experiments it was found that the active principle could bind to both erythrocytes and lymphocytes and could spontaneously elute from these cells onto labeled lymphocytes which were then unable to home efficiently. The data suggest that Bordetella pertussis-induced lymphocytosis involves a reversible attachment of the pertussis factor onto the surfaces of lymphocytes which prevents their recirculation to lymphoid organs. Recirculating lymphocytes are presumably affected as they emerge from lymphoid organs to enter the blood.

1. Leukocytosis- and lymphocytosis-stimulating activity was present in fluid cultures of B. pertussis. The activity was found primarily in the culture supernatant fluid. 2. The sequential changes in the leukocyte response were similar to those previously observed following injection of intact bacteria into mice. 3. Activity was destroyed by heat and was diminished, but not abolished, by prolonged treatment with proteolytic enzymes. 4. A water-insoluble fraction of the culture supernatant fluid was isolated which contained virtually all of the activity. The specific activity was more than 100-fold greater than that of the intact bacteria, and injection of microgram quantities produced a response. 5. The distribution of histamine-sensitizing factor followed that of leukocytosis-stimulating activity. In contrast, mouse protective antigen was localized to the bacterial pellet.

Understanding fracture initiation and propagation from perforated wellbores is essential to designing a perforation scheme to achieve an efficient hydraulic fracture stimulation treatment. The effect of perforation design on hydraulic fracture propagation has been extensively studied using experimental and analytical methods. Because the experimental investigation of hydraulic fracture is complicated, expensive, and often returns limited results, numerical methods can be applied as an efficient way to simulate fracture propagation from perforations. An Extended Finite Element Method (XFEM) was used to develop a model to investigate the effects of various parameters on fracture propagation from a set of perforations. These parameters included perforation orientation, perforation length, stress anisotropy, and elastic properties of the formation. Fracture propagation patterns from the XFEM model were first matched against published experimental studies and exhibited good agreement. The model was then used to broaden the study of perforation effects. Results of the modeling proved the effects of perforation orientation and length on hydraulic fracture propagation pattern. Horizontal stress anisotropy and rock mechanical properties were observed to strongly influence fracture propagation. It was also observed that, when two or more perforations are positioned at different orientation angles at the same depth, a fracture tends to propagate from the less deviated perforation. In these cases, the more deviated perforation can develop a short fracture, following a propagating pattern that could be caused by stress shadowing/interference. Stress interference between two perforations positioned closely together results in either perforation breakdown or fracture propagating away from one another. The simulation results from this study offer methods to enhance perforation design for hydraulic fracture treatment, particularly in the case of high stress anisotropy and high uncertainty in a preferred fracture plane. Analyzing competing perforations suggests that a technique based on this concept can be applied when high uncertainty exists regarding the direction of the principal horizontal stresses through increasing perforation density.

1. Joe B. Wyatt Distinguished University Professor, New York Alumni Chancellor’s Chair in Law, and Professor of Biological Sciences, Vanderbilt University, Director, MacArthur Foundation Research Network on Law and Neuroscience 2. Harrison Foundation Professor of Medicine and Law, Professor of Psychiatry and Neurobehavioral Sciences, Director, Institute of Law, Psychiatry and Public Policy, Professor of Public Policy, Frank Batten School of Leadership and Public Policy, University of Virginia 3. Sackler Professor for Developmental Psychobiology, Director, Sackler Institute, Weill Cornell Medical College 4. Judge, United States Court of Appeals for the Fourth Circuit 5. John F. Digardi Distinguished Professor of Law, Director of the UCSF/UCHastings Consortium on Law, Science H Stanford University 15. Professor of Law, Professor of Philosophy & Psychology, Yale University ∗Corresponding author. E-mail: owen.jones@vanderbilt.edu

Invaluable to both well stimulation and wellbore stability is the study of fracture initiation and propagation. The literature is rich with fracture tip phenomena theories. In particular, the effect of tip plasticity has been the subject of much debate. However, little has been done to investigate the effect of rock mass plasticity, a potential controlling factor in weak and compactible rocks. This paper advances a 3D dynamic computational model to replicate the growth of hydraulic fractures in elastoplastic rocks. The proposed model is based on a non-linear Finite Element formulation that couples solid deformation and fluid flow. Rock is treated as a work-hardening elastoplastic material whose plastic deformation can be found using an associated flow rule. This paper features a new computational method to find material tangent stiffness tensor in non-linear Finite Element Analysis. A meshing/remeshing scheme is employed to maintain a high mesh resolution and to reach infinite boundary effect while keeping simulation runtime reasonable. The model tested successfully against analytical solutions for pressurized cracks and radially growing hydraulic fractures. Due to the action of fracturing fluid pressure on fracture faces, normal stress increases on the fracture faces and a zone of tensile stress forms ahead of the fracture. The size of this zone dictates fracture growth rate. Due to plastic deformation, when subjected to loading, compared to elastic rocks, elastoplastic rocks experience less increase in normal stress on the fracture face and a smaller tensile zone. Combined with typically high permeability of compactible rocks, this results in slower fracture growth, larger fracture widths and higher fracture pressures. Another significant observation is that elastoplastic rocks can undergo shear localization, depending on rock properties, stress state and treatment conditions. This paper presents a unique method to account for rock mass plasticity during fracturing operations. It showcases a robust 3D computational non-linear Finite Element model with a concrete physical foundation. Simulation results are in agreement with both laboratory and field observations.

Water is one of the most critical and costly life support elements, even under the most stringent water use approaches. Technologies that can increase the sustainability of water processing by reducing expendables and helping to close the water loop can have large impacts on mission costs. Current technologies for water processing are intensive users of resources, including power for processes such as distillation, and consumables for preand post-treatment. In particular, urine pre-processing requires the continuous consumption of hazardous and corrosive chemicals. Further, current recovery rates are limited partly by the chemical pre-processing, and the brine produced from this pre-treated chemical is challenging to process. Biological pre-treatment may offer substantial efficiencies over traditional technologies, and offer secondary benefits with only minor costs. For the past 9 months, we have operated a TRL 5 membrane aerated bioreactor processing an extended habitation waste stream (urine/hygiene/humidity condensate). The reactor has successfully processed the wastewater at loading rates of 20 L/d and 30 L/d and is currently being challenged at 40 L/d. The reactor has exceeded 70% NH4 + conversion, 86% DOC conversion, 55% TN reduction, and maintained a pH < 7. Conversion rates for NH4 + and DOC are approaching 1 g/m 2 -d. Finally, preliminary gas phase measurements reveal that the total O2 consumption is ~100 g/d, while CO2 production was ~ 4g/d and N2 production was estimated at 20 g/d (~13 L/d).

How should one think and write about criminal law? Leo Katz and C.L. Ten have written thoughtful, instructive, and interesting books about substantive criminal law that do not discuss one substantive issue in common Katz addresses primarily doctrinal puzzles, Ten addresses primarily general justifying theories. Nevertheless, the books have many similarities. Both authors take the world as they find it: neither suggests that there is anything fundamentally wrong with current law. Both virtually exclude from consideration the "crime problem" and the administration of criminal justice. Both are fond of and attempt to justify the usefulness of unusual or fanciful hypotheticals to make their points. Both demonstrate the value, indeed the necessity, of using theories and data from other disciplines, mostly analytic philosophy, to make coherent sense of Anglo-American criminal law. Together they offer an encompassing examination of present criminal law.

The relative mobilities of six enzymes from the trophozoites of five axenically-cultured isolates of Giardia from human, cat, and guinea pig hosts were compared by starch and polyacrylamide gel electrophoresis. The six enzymes compared were malate dehydrogenase (NAD+) (MDH) (EC 1.1.1.37), malate dehydrogenase (decarboxylating) (ME) (EC 1.1.1.40), hexokinase (EC 2.7.1.1), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), glucose-6-phosphate dehydrogenase (G6P) (EC 1.1.1.49), and alpha-glycerophosphate dehydrogenase (EC 1.1.1.8). The latter three enzymes have not been previously reported in Giardia. On the basis of zymogram patterns, the five Giardia isolates were divided into three zymodemes. Zymodeme I comprised human-1/England, human-1/Bethesda, and cat-1/Portland, Zymodeme II the guinea pig-1/Portland isolate, and Zymodeme III the human-1/Portland isolate. These zymodemes were further substantiated when several physical and kinetic properties of three of the enzymes, MDH, ME, and G6P, were examined. Our results, in which Giardia isolated from different mammalian hosts share multiple isoenzymes, question the validity of the practice of assigning Giardia species names on the basis of the animal host from which the protozoan was obtained.

Excerpt Whooping cough at the turn of the century was a major factor in infant morbidity and mortality in the United States. The attack rate in family epidemics was extraordinarily high and often g...

Excerpt Pulmonary paragonimiasis has rarely been studied in the United States. The case to be presented, the first admitted to the Columbia-Presbyterian Medical Center, afforded an unusual opportun...