bluuebunny/crossref_metadata_2025 huggingface dataset:
The Solvability of the Decision Problem for Classes of Proper Formulas and Related Results
Authors: Di Paola Robert A.
Published: July 2002

In connection with the development of an actual question-answering system, the Relational Data File of The Rand Corporation, a class of formulas of the predicate calculus, the definite formulas of Kuhns, was proposed as the class of symbolic representations of the “reasonable” questions to put to this retrieval system. Roughly speaking, the definite formulas are those formulas
F
such that the set of true substitution instances of
F
in a finite interpretation
I
are preserved on passage to a certain special extension
I
′ of
I
. The proper formulas are those definite formulas which are supposedly especially suitable for machine processing. It has previously been shown by the author that the decision problem for the class of definite formulas is recursively unsolvable. In this paper, however, it is shown that the decision problem for various classes of proper formulas is solvable. Thus, for each of these classes there is a mechanical procedure to decide of an arbitrary formula whether it is a member of the class. It follows that for each of these classes there is no effective transformation
@@@@ which takes an arbitrary definite formula
F
into a proper equivalent @@@@(
F
). In addition, it is shown that the decision problems for a number of classes of formulas which bear a structural similarity to any class of proper formulas are recursively unsolvable.
Optimal Covering Algorithms in Methods of Search for Solving Polynomial Equations
Authors: Friedli Armin
Published: July 2002

Covering algorithms utilized in methods of search for finding zeros of complex polynomials are investigated from both a deterministic and a probabilistic point of view.
q
-coverings are found to be optimal, and numerical examples of this and other types of coverings are given.
On the Correctness of Semantic-Syntax-Directed Translations
Authors: Krishnaswamy Ramachandran , Pyster Arthur B.
Published: July 2002

The correctness of semantic-syntax-directed translators (SSDTs) is examined. SSDTs are a generalization of syntax-directed translators in which semantic information is employed to partially direct the translator. Sufficient conditions for an SSDT to be “semantic-preserving,” or “correct,” are presented. A further result shows that unless certain conditions are met, it is undecidable, in general, whether an SSDT is semantic-preserving.
The RISC BLAS
Authors: Daydé Michel J. , Duff Iain S.
Published: July 2002

We describe a version of the Level 3 BLAS which is designed to be efficient on RISC processors. This is an extension of previous studies by the authors and colleagues on a similar approach for efficient serial and parallel implementations on virtual-memory and shared-memory multiprocessors. All our codes are written in Fortran and use loop-unrolling, blocking, and copying to improve the performance. A blocking technique is used to express the BLAS in terms of operations involving triangular blocks and calls to the matrix-matrix multiplication kernel (GEMM). No manufacturer-supplied or assembler code is used. This blocked implementation uses the same blocking ideas as in our implementation for vector machines except that the ordering of loops is designed for efficient reuse of date held in cache and not necessarily for parallelization. All the codes are specifically tuned for RISC processors. The software also includes a tuned version of GEMM. A parameter which controls the blocking allows efficient exploitation of the memory hierarchy on the various target computers. We present results on a range of RISC-based workstations and multiprocessors: CRAY T3D, DEC 8400 5/300, HP 715/64, IBM SP2, MEIKO CS2-HA, SGI Power Challenge 10000, and SUN UltraSPARC-1 model 140. This implementation of the Level 3 BLAS is available on anonymous FTP, and we welcome input from users to improve and extend our BLAS implementation.
A model for compound type changes encountered in schema evolution
Authors: Lerner Barbara Staudt
Published: July 2002

Schema evolution is a problem that is faced by long-lived data. When a schema changes, existing persistent data can become inaccessible unless the database system provides mechanisms to access data created with previous versions of the schema. Most existing systems that support schema evolution focus on changes local to individual types within the schema, thereby limiting the changes that the database maintainer can perform. We have developed a model of type changes involving multiple types. The model describes both type changes and their impact on data by defining derivation rules to initialize new data based on the existing data. The derivation rules can describe local and nonlocal changes to types to capture the intent of a large class of type change operations. We have built a system called Tess (Type Evolution Software System) that uses this model to recognize type changes by comparing schemas and then produces a transformer that can update data in a database to correspond to a newer version of the schema.
Subgoal induction
Authors: Morris James H. , Wegbreit Ben
Published: July 2002

A proof method, subgoal induction, is presented as an alternative or supplement to the commonly used inductive assertion method. Its major virtue is that it can often be used to prove a loop's correctness directly from its input-output specification without the use of an invariant. The relation between subgoal induction and other commonly used induction rules is explored and, in particular, it is shown that subgoal induction can be viewed as a specialized form of computation induction. A set of sufficient conditions are presented which guarantee that an input-output specification is strong enough for the induction step of a proof by subgoal induction to be valid.
Proving monitors
Authors: Howard John H.
Published: July 2002

Interesting scheduling and sequential properties of monitors can be proved by using state variables which record the monitors' history and by defining extended proof rules for their wait and signal operations. These two techniques are defined, discussed, and applied to examples to prove properties such as freedom from indefinitely repeated overtaking or unnecessary waiting, upper bounds on queue lengths, and historical behavior.
Perturbations of eigenvalues of non-normal matrices
Authors: van der Sluis A.
Published: July 2002

The problem considered is to give bounds for finite perturbations of simple and multiple eigenvalues λ

i

of nonnormal matrices, where these bounds are in terms of the eigenvalues {λ

i

}, the departure from normality
σ
, and the Frobenius norm ‖ Δ
A
‖

F

of the perturbation matrix, but not in terms of the eigensystem. The bounds which are derived are shown to be almost attainable for any set of all matrices of given {λ

i

} and
σ
. One conclusion is that, very roughly speaking, a simple eigenvalue λ
1
is perturbed by |Δλ
1
| ≲ ‖ Δ
A
‖

F

· ∏ (
σ
/

θ
j

) where

θ
j

is of the order of magnitude of |λ
1
- λ

j

|, the product being extended over all
j
where

θ
j

≲
σ
.
Music and computer composition
Authors: Moorer James Anderson
Published: July 2002

The problem discussed is that of simulating human composition of Western popular music by computer and some relevant theories of music and harmony are given. Problems with this kind of program and several schemes that are known not to work are discussed. Several previous computer compositions are discussed, including the ILLIAC Suite.

A program to generate short melody fragments was written to simulate some of the aspects of human composition. Five samples of its output are presented and discussed. It was discovered that although the fragments show many of the characteristics of popular melodies, they have a strangely alien sound. It is theorized that this is because the relevant probabilities which would discriminate against unfamiliar sequences were not used.
SAFKASI
Authors: Wallach Dan S. , Appel Andrew W. , Felten Edward W.
Published: July 2002

In order to run untrusted code in the same process as trusted code, there must be a mechanism to allow dangerous calls to determine if their caller is authorized to exercise the privilege of using the dangerous routine. Java systems have adopted a technique called stack inspection to address this concern. But its original definition, in terms of searching stack frames, had an unclear relationship to the actual achievement of security, overconstrained the implementation of a Java system, limited many desirable optimizations such as method inlining and tail recursion, and generally interfered with interprocedural optimization. We present a new semantics for stack inspection based on a belief logic and its implementation using the calculus of
security-passing style
which addresses the concerns of traditional stack inspection. With security-passing style, we can efficiently represent the security context for any method activation, and we can build a new implementation strictly by rewriting the Java bytecodes before they are loaded by the system. No changes to the JVM or bytecode semantics are necessary. With a combination of static analysis and runtime optimizations, our prototype implementation showes reasonable performance (although traditional stack inspection is still faster), and is easier to consider for languages beyond Java. We call our system SAFKASI (the Security Architecture Formerly Known as Stack Inspection).
Specialization tools and techniques for systematic optimization of system software
Authors: McNamee Dylan , Walpole Jonathan , Pu Calton , Cowan Crispin , Krasic Charles , Goel Ashvin , Wagle Perry , Consel Charles , Muller Gilles , Marlet Renauld
Published: July 2002

Specialization has been recognized as a powerful technique for optimizing operating systems. However, specialization has not been broadly applied beyond the research community because current techniques based on manual specialization, are time-consuming and error-prone. The goal of the work described in this paper is to help operating system tuners perform specialization more easily. We have built a specialization toolkit that assists the major tasks of specializing operating systems. We demonstrate the effectiveness of the toolkit by applying it to three diverse operating system components. We show that using tools to assist specialization enables significant performance optimizations without error-prone manual modifications. Our experience with the toolkit suggests new ways of designing systems that combine high performance and clean structure.
The intuitionism behind Statecharts steps
Authors: Lüttgen Gerald , Mendler Michael
Published: July 2002

The semantics of Statecharts macro steps, as introduced by Pnueli and Shalev [1991], lacks compositionality. This article first analyzes the compositionality problem and traces it back to the invalidity of the Law of the Excluded Middle. It then characterizes the semantics via a particular class of linear intuitionistic Kripke models. This yields, for the first time in the literature, a simple fully abstract semantics that interprets Pnueli and Shalev's concept of failure naturally. The results not only give insight into the semantic subtleties of Statecharts, but also provide a basis for an implementation, for developing algebraic theories for macro steps, and for comparing different Statecharts variants.
Collocation software for second-order elliptic partial differential equations
Authors: Houstis E. N. , Mitchell W. F. , Rice J. R.
Published: July 2002

We consider the collocation method for linear, second-order elliptic problems on rectangular and general two-dimensional domains. An overview of the method is given for general domains, followed by a discussion of the improved efficiencies and simplifications possible for rectangular domains. A very-high-level description is given of three specific collocation algorithms that use Hermite bicubic basic functions, (1) GENCOL (collocation on general two-dimensional domains), (2) HERMCOL (collocation on rectangular domains with general linear boundary conditions), and (3) INTCOL (collocation on rectangular domains with uncoupled boundary conditions). The linear system resulting from INTCOL has half the bandwidth of that from HERMCOL, which provides substantial benefit in solving the system. We provide some examples showing the range of applicability of the algorithms and some performance profiles illustrating their efficiency. Fortran implementations of these algorithms are given in the companion papers [10, 11].
IMPORT AND ROUTING OF NUCLEUS-ENCODED CHLOROPLAST PROTEINS
Authors: Cline Kenneth , Henry Ralph
Published: July 2002

▪ Abstract  Most chloroplast proteins are nuclear encoded, synthesized as larger precursor proteins in the cytosol, posttranslationally imported into the organelle, and routed to one of six different compartments. Import across the outer and inner envelope membranes into the stroma is the major means for entry of proteins destined for the stroma, the thylakoid membrane, and the thylakoid lumen. Recent investigations have identified several unique protein components of the envelope translocation machinery. These include two GTP-binding proteins that appear to participate in the early events of import and probably regulate precursor recognition and advancement into the translocon. Localization of imported precursor proteins to the thylakoid membrane and thylakoid lumen is accomplished by four distinct mechanisms; two are homologous to bacterial and endoplasmic reticulum protein transport systems, one appears unique, and the last may be a spontaneous mechanism. Thus chloroplast protein targeting is a unique and surprisingly complex process. The presence of GTP-binding proteins in the envelope translocation machinery indicates a different precursor recognition process than is present in mitochondria. Mechanisms for thylakoid protein localization are in part derived from the prokaryotic endosymbiont, but are more unusual and diverse than expected.
Recent Developments in Molecular Genetics of Candida Albicans
Authors: De Backer Marianne D. , Magee Paul T. , Pla Jesus
Published: July 2002

▪ Abstract  The frequency of opportunistic infections caused by the fungus Candida albicans is very high and is expected to continue to increase as the number of immunocompromised patients rises. Research initiatives to study the biology of this organism and elucidate its pathogenic determinants have therefore expanded significantly during the last 5–10 years. The past few years have also brought continuous improvement in the techniques to study gene function by gene inactivation and by regulated gene expression and to study gene expression and protein localization by using gene reporter systems. As steadily more genomic sequence information from this human fungal pathogen becomes available, we are entering a new era in antimicrobial research. However, many of the currently available molecular genetics tools are poorly adapted to a genome-wide functional analysis in C. albicans, and further development of these tools is hampered by the asexual and diploid nature of this organism. This review outlines recent advances in the development of molecular tools for functional analysis in C. albicans and summarizes current knowledge about the genomic and genetic variability of this important human fungal pathogen.
Chemistry and Microphysics of Polar Stratospheric Clouds and Cirrus Clouds
Authors: Zondlo Mark A. , Hudson Paula K. , Prenni Anthony J. , Tolbert Margaret A.
Published: July 2002

Ice particles found within polar stratospheric clouds (PSCs) and upper tropospheric cirrus clouds can dramatically impact the chemistry and climate of the Earth's atmosphere. The formation of PSCs and the subsequent chemical reactions that occur on their surfaces are key components of the massive ozone hole observed each spring over Antarctica. Cirrus clouds also provide surfaces for heterogeneous reactions and significantly modify the Earth's climate by changing the visible and infrared radiation fluxes. Although the role of ice particles in climate and chemistry is well recognized, the exact mechanisms of cloud formation are still unknown, and thus it is difficult to predict how anthropogenic activities will change cloud abundances in the future. This article focuses on the nucleation, chemistry, and microphysical properties of ice particles composing PSCs and cirrus clouds. A general overview of the current state of research is presented along with some unresolved issues facing scientists in the future.
ELECTRONTRANSMISSIONTHROUGHMOLECULES ANDMOLECULARINTERFACES
Authors: Nitzan Abraham
Published: July 2002

▪ Abstract  Electron transmission through molecules and molecular interfaces has been a subject of intensive research due to recent interest in electron-transfer phenomena underlying the operation of the scanning-tunneling microscope on one hand, and in the transmission properties of molecular bridges between conducting leads on the other. In these processes, the traditional molecular view of electron transfer between donor and acceptor species gives rise to a novel view of the molecule as a current-carrying conductor, and observables such as electron-transfer rates and yields are replaced by the conductivities, or more generally by current-voltage relationships, in molecular junctions. Such investigations of electrical junctions, in which single molecules or small molecular assemblies operate as conductors, constitute a major part of the active field of molecular electronics. In this article I review the current knowledge and understanding of this field, with particular emphasis on theoretical issues. Different approaches to computing the conduction properties of molecules and molecular assemblies are reviewed, and the relationships between them are discussed. Following a detailed discussion of static-junctions models, a review of our current understanding of the role played by inelastic processes, dephasing and thermal-relaxation effects is provided. The most important molecular environment for electron transfer and transmission is water, and our current theoretical understanding of electron transmission through water layers is reviewed. Finally, a brief discussion of overbarrier transmission, exemplified by photoemission through adsorbed molecular layers or low-energy electron transmission through such layers, is provided. Similarities and differences between the different systems studied are discussed.
ANIMAL ADAPTATIONS FOR TOLERANCE AND EXPLOITATION OF POISONOUS SULFIDE
Authors: Grieshaber Manfred K. , Völkel Susanne
Published: July 2002

▪ Abstract  Many aquatic animal species can survive sulfide exposure to some extent through oxidation of the sulfide, which results mainly in thiosulfate. In several species, sulfide oxidation is localized in the mitochondria and is accompanied by ATP synthesis. In addition, blood-based and intracellular compounds can augment sulfide oxidation. The formation of thiosulfate requires oxygen, which results in an increase in oxygen consumption of some species. If not all sulfide is detoxified, cytochrome c oxidase is inhibited. Under these conditions, a sulfide-dependent anaerobic energy metabolism commences.
Prediction of Outcomes in Hypertensive Patients With Suspected Coronary Disease
Authors: Marwick Thomas H. , Case Colin , Sawada Stephen , Vasey Charles , Thomas James D.
Published: July 2002

Stress echocardiography has been shown to improve the diagnosis of coronary artery disease in the presence of hypertension, but its value in prognostic evaluation is unclear. We sought to determine whether stress echocardiography could be used to predict mortality in 2363 patients with hypertension, who were followed for up to 10 years (mean 4.0±1.8) for death and revascularization. Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were confined to one territory in 489 patients (21%) and to multiple territories in 365 patients (15%). Cardiac death was less frequent among the patients able to exercise than among those undergoing dobutamine echocardiography (4% versus 7%,
P
< 0.001). The risk of death in patients with a negative stress echocardiogram was <1% per year. Ischemia identified by stress echocardiography was an independent predictor of mortality in those able to exercise (hazard ratio 2.21, 95% confidence intervals 1.10 to 4.43,
P
=0.0001) as well as those undergoing dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75,
P
=0.0001); other predictors were age, heart failure, resting LV dysfunction, and the Duke treadmill score. In stepwise models replicating the sequence of clinical evaluation, the results of stress echocardiography added prognostic power to models based on clinical and stress-testing variables. Thus, the results of stress echocardiography are an independent predictor of cardiac death in hypertensive patients with known or suspected coronary artery disease, incremental to clinical risks and exercise results.
The Role of Perceptual Load in Neglect: Rejection of Ipsilesional Distractors is Facilitated with Higher Central Load
Authors: Lavie Nilli , Robertson Ian H.
Published: July 2002

Neglect is known to produce a bias towards the ipsilesional side. Here we examined whether this bias is automatic or can be modulated by manipulating perceptual load in a relevant task [e.g., Lavie, N. (1995). Perceptual load as a necessary condition for selective attention. Journal of Experimental Psychology: Human Perception and Performance, 21, 451–468]. Three patients with left neglect and three healthy controls made speeded choice responses to a target letter in the center of the display while attempting to ignore an irrelevant distractor presented on left or right. Perceptual load was manipulated by inducing a search for the target that appeared with another central stimulus, which was either a blob (low load) or a nontarget letter (higher load). Response competition effects from ipsilesional distractors were significantly reduced by higher load. The same increase of load, however, did not decrease distractor effects in the control group, as expected [e.g., Lavie, N., & Cox, S. (1997). On the efficiency of attentional selection: Efficient visual search results in inefficient rejection of distraction. Psychological Science, 8, 395-398]. These results demonstrate that ipsilesional bias in neglect is not fully automated and emphasize an additional restriction of perceptual capacity. Moreover, they supported our prediction that reduced perceptual capacity in neglect can lead to improved distractor rejection with just small increases in perceptual load.
Residual Vision in a Subject with Damaged Visual Cortex
Authors: Schärli Heinz , Harman Alison M. , Hogben John H.
Published: July 2002

It is well known that a lesion in the optic radiation or striate cortex leads to blind visual regions in the retinotopically corresponding portion of the visual field. However, various studies show that some subjects still perceive certain stimuli even when presented in the “blind” visual field. Such subjects either perceive stimuli abnormally or only certain aspects of them (residual vision) or, in some cases, deny perception altogether even though visual performance can be shown to be above chance (blindsight). Research on monkeys has suggested a variety of parallel extrastriate visual pathways that could bypass the striate cortex and mediate residual vision or blindsight. In the present study, we investigated a subject with perimetrically blind visual areas caused by bilateral brain damage. Black and white stimuli were presented at many locations in the intact and affected areas of the visual field. The subject's task was to state, using confidence levels, whether the target stimulus was black or white. The results revealed an area in the “blind” visual field in which the subject perceived a light flash when the experimental black stimulus was presented. We hypothesize that a spared region in the visual cortex most likely accounts for these findings.
Approximate Maximum Entropy Joint Feature Inference Consistent with Arbitrary Lower-Order Probability Constraints: Application to Statistical Classification
Authors: Miller David J. , Yan Lian
Published: July 2002

We propose a new learning method for discrete space statistical classifiers. Similar to Chow and Liu (1968) and Cheeseman (1983), we cast classification/inference within the more general framework of estimating the joint probability mass function (p.m.f.) for the (feature vector, class label) pair. Cheeseman's proposal to build the maximum entropy (ME) joint p.m.f. consistent with general lower-order probability constraints is in principle powerful, allowing general dependencies between features. However, enormous learning complexity has severely limited the use of this approach. Alternative models such as Bayesian networks (BNs) require explicit determination of conditional independencies. These may be difficult to assess given limited data. Here we propose an approximate ME method, which, like previous methods, incorporates general constraints while retaining quite tractable learning. The new method restricts joint p.m.f. support during learning to a small subset of the full feature space. Classification gains are realized over dependence trees, tree-augmented naive Bayes networks, BNs trained by the Kutato algorithm, and multilayer perceptrons. Extensions to more general inference problems are indicated. We also propose a novel exact inference method when there are several missing features.
Gene Expression and Fast Construction of Distributed Evolutionary Representation
Authors: Kargupta Hillol , Park Byung-Hoon
Published: July 2002

The gene expression process in nature produces different proteins in different cells from different portions of the DNA. Since proteins control almost every important activity in a living organism, at an abstract level, gene expression can be viewed as a process that evaluates the merit or “fitness” of the DNA. This distributed evaluation of the DNA would not be possible without a decomposed representation of the fitness function defined over the DNAs. This paper argues that, unless the living body was provided with such a representation, we have every reason to believe that it must have an efficient mechanism to construct this distributed representation. This paper demonstrates polynomial-time computability of such a representation by proposing a class of efficient algorithms. The main contribution of this paper is two-fold. On the algorithmic side, it offers a way to scale up evolutionary search by detecting the underlying structure of the search space. On the biological side, it proves that the distributed representation of the evolutionary fitness function in gene expression can be computed in polynomial-time. It advances our understanding about the representation construction in gene expression from the perspective of computing. It also presents experimental results support-ing the theoretical performance of the proposed algorithms.
Oxygen and the Trade-off between Egg Ventilation and Brood Protection in the Common Goby
Authors: Jones Jackie , Reynolds John
Published: July 2002

1. We examined compromises between defence of nests against predation and ventilation of eggs in the common goby (Pomatoschistus microps). Females are known to prefer nests with small entrances, which are less vulnerable to predatory shore crabs, Carcinus maenus. However, small nest entrances may hamper egg ventilation by males. This may be especially detrimental under conditions of low dissolved oxygen. 2. Males did not make smaller entrances to their nests when in the presence of predatory crabs, but they had larger entrances under low oxygen than in normal oxygen levels. 3. Males diverted time from ventilating nests to attacking crabs. 4. Thus, males exchanged direct care of the eggs for protection against predators by reducing their fanning activity, but not according to needs of their eggs for oxygenation. This trade-off may therefore impose a greater cost to egg survival for males in low oxygen.
Temperature-induced morphometrical variability in an isolate of Pratylenchus vulnus Allen & Jensen, 1951 (Nematoda: Tylenchida)
Authors: Doucet Marcelo , Baujard Pierre , Pinochet Jorge , Di Rienzo Julio , Lax Paola
Published: July 2002

The influence of temperature on morphometrical variability of females and males of an isolate of Pratylenchus vulnus was studied. Nematodes were reared monoxenically on carrot disk cultures and incubated for 4 months at 16, 21, 25 and 28°C. The morphometrics of several characters were significantly affected depending on sex and temperature. It is concluded that temperature can significantly influence several morphometrical characters of P.vulnus.
Surface temperature, sequence stratigraphy and deep burial diagenesis
Authors: Worden R. H. , Ruffell A. H. , Cornford C.
Published: July 2002

Fourth-order relative sea level changes may have a significant impact upon burial diagenesis and reservoir quality through their effect upon surface and subsurface temperature. Relative sea level changes can induce sediment surface temperature changes of <20°C when the sediment surface changes from being close to or beneath the thermocline to being sub-aerially exposed. Such sea level changes typically occur on a timescale of half a million years. Approximately one quarter to one third of the magnitude of these temperature fluctuations will be propagated to 2500 m in the subsurface. Shorter timescale fluctuations of similar magnitude, resulting from glaciation, will not be significant below ~1000 m burial as there is not enough time to effect the change before the next surface temperature cycle occurs. Diagenesis is strongly controlled by temperature through its impact on the driving force and rate of geochemical processes. Burial diagenesis and cementation may thus be episodic on timescales associated with sequence stratigraphic events occurring on the surface, thousands of metres above the zone where diagenesis is occurring.
Expandability- layer stacking relationship during experimental alteration of a Wyoming bentonite in pH 13.5 solutions at 35 and 60°C
Authors: Rassineux F. , Griffault L. , Meunier A. , Berger G. , Petit S. , Vieillard P. , Zellagui R. , Munoz M.
Published: July 2002

The reaction of a Wyoming-type bentonite with pH 13.5 solutions was investigated experimentally at 35 and 60°C for periods of 1 to 730 days. Some crystal properties of the starting montmorillonitic clay remain unchanged, i.e. stability of the octahedral sheet, total cation exchange capacity (CEC) and CEC after neutralization of the octahedral charge, full expandability in the Casaturated state, and size distribution. Other properties are changed, e.g. there is an increase in the expandability after octahedral charge neutralization; a slight increase in the average layer charge; a decrease of the total surface area; and a particle morphological change from flakes to hexagonal shape.

The composition and the structure of the smectite layers did not change significantly during the reaction. The increasing number of expandable layers after octahedral charge neutralization is attributed to modifications in the stacking sequence. The number of interlayers surrounded by two charged tetrahedral sheets increases with reaction time.
Smectite to illite conversion by hydrous pyrolysis
Authors: Roaldset E. , Wei He , Grimstad S.
Published: July 2002

Experimental illitization of smectite has been simulated by means of hydrous pyrolysis, using a smectite-rich starting material from a Lower Tertiary claystone from the Oseberg field, North Sea. The <2 µm fraction was subjected to hydrous pyrolysis using KCL solutions at concentrations of 1.0 and 0.01 N, temperatures from 180-350°C and reaction times from 24-72 h. The conversion of smectite into illite has been identified by XRD analysis of the pyrolysed products. It was clearly demonslrated that the K+ concentration ([K+]) and temperature are the major factors controlling the rate and extent of illitization. The distributions of activation energies around 33 kcal/mol and frequency factors in the range of 10+8 to 10+9 S-1 have been calculated by applying a parallel reaction model. However, geological modelling and comparison with buried smectite clays indicates that both 1.0 n and 0.01 N KCL are too high in K+ content compared to the pore-water. The results suggest that dilute KCL solution close to pore-water should be used in hydrous pyrolysis to obtain proper kinetic models.
Fundamental particles: an informal history
Authors: Nadeau P. H.
Published: July 2002

An informal overview is given of the development of the fundamental particle model, where, in a series of papers published from 1982-1987, researchers from the Macaulay Institute presented a radical model for the interpretation of the crystal structure, chemistry, and genesis of interstratified clays. The model reconciled electron microscopy and X-ray diffraction (XRD) data from a variety of sedimentary clay specimens, and proposed that these minerals were composed of nano-crystalline ‘fundamental particles’ whose adsorptive interfaces were responsible for the expanding smectite layers observed by XRD. The term ‘interparticle diffraction’ was used to describe this phenomenon. Experiments were reported which proved the model, by producing randomly interstratified illite-smectites from combinations of ordered illite-smectite and smectite clay dispersions. The model was extended to propose that fundamental particles were the primary units of crystallization, and that changes in the particle population were responsible for the commonly observed evolution in XRD character of these minerals with increasing depth of burial and temperature.
Factors influencing the development of an anti–factor IX (FIX) immune response following administration of adeno-associated virus–FIX
Authors: Ge Ying , Powell Sandra , Van Roey Melinda , McArthur James G.
Published: July 2002

The present study sought to determine the impact of the route of administration of an adeno-associated virus (AAV) vector encoding human factor IX (hFIX) on the induction of an immune response against the vector and its xenogenic transgene product, hFIX. Increasing doses of AAV-hFIX were administered by different routes to C57Bl/6 mice, which typically demonstrate significant immune tolerance to hFIX. The route of delivery had a profound impact on serum hFIX levels as well as the induction of an anti-hFIX humoral immune response. At all dose levels tested, delivery of AAV-hFIX by an intramuscular (IM) route induced an antibody response against the human FIX protein and no hFIX was detected in the serum of animals even at doses of 2 × 1011 DNA viral particles (vp) of AAV-hFIX. This was in stark contrast to the mice that received AAV-hFIX by intraportal vein (IPV) administration. No anti-hFIX inhibitors were observed in any of these mice and therapeutic levels of hFIX were detected in the serum of all mice that received doses of 2 × 1010 vp AAV-hFIX and higher. When pre-existing neutralizing immunity to AAV was established in mice, AAV-hFIX administration by either the IM or IPV routes did not result in detectable serum hFIX. Although hFIX expression was not observed in mice with pre-existing neutralizing immunity to AAV, an anti-hFIX response was induced in all of the animals that received AAV-hFIX by the IM route. This was not observed in the preimmune mice that received AAV-hFIX by IPV administration. These results suggest that the threshold of inducing an immune response against a secreted transgene product, in this case the xenoprotein hFIX, is lower when the vector is administered by the IM route even in animals with pre-existing immunity to AAV.
Human equivalent of the mouse Nude/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation
Authors: Pignata Claudio , Gaetaniello Lucia , Masci Anna Maria , Frank Jorge , Christiano Angela , Matrecano Eliana , Racioppi Luigi
Published: July 2002

Human Nude/SCID (severe combined immunodeficiency) is the first severe combined immunodeficiency caused by mutation of the winged–helix–nude (WHN) gene, which is expressed in the thymus but not in the hematopoietic lineage. The disease is characterized by a T-cell defect, congenital alopecia, and nail dystrophy. A Nude/SCID patient who underwent bone marrow transplantation from the human leukocyte antigen–identical heterozygote brother was studied to investigate, in this unique model, the role of the thymus in immunologic reconstitution. Despite an increase in CD3+, CD4+, and CD8+cells, CD4+ CD45 RA naive lymphocytes were not regenerated. Conversely, naive CD8+ cells were normal. After an initial recovery, lymphocyte proliferation to mitogens progressively declined compared with controls and genotypically identical donor cells grown in the WHN+/−environment. Analysis of the T-cell receptor (TCR) repertoire of CD4+ cells revealed that only 3 of 18 Vβ families had an altered CDR3 heterogeneity length profile. Conversely, CD8+lymphocytes showed an abnormal distribution in most Vβ families. These data indicate that the thymus is differentially required in the reconstitution of CD4+ and CD8+ naive subsets and in the maintenance of their TCR repertoire complexity. Taken together, these findings suggest that bone marrow transplantation is ineffective in the long-term cure of this form of SCID.
Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor SCH66336
Authors: Reichert Anja , Heisterkamp Nora , Daley George Q. , Groffen John
Published: July 2002

The Philadelphia (Ph) chromosome is found in approximately 3% of pediatric patients with acute lymphoblastic leukemia (ALL) and the percentage markedly increases in adult patients. The prognosis for this class of patients is poor, and no standard chemotherapy combination so far has demonstrated long-term efficacy. The Ph-translocation joins theBCR and ABL genes and leads to expression of a chimeric Bcr/Abl protein with enhanced tyrosine kinase activity. This increase in activity leads to malignant transformation by interference with basic cellular functions such as the control of proliferation, adherence to stroma and extracellular matrix, and apoptosis. One important pathway activated by Bcr/Abl is the Ras pathway. Ras proteins have to undergo a series of posttranslational modifications to become biologically active. The first modification is the farnesylation of the C-terminus catalyzed by farnesyl transferase. We studied the effect of the farnesyl transferase inhibitor SCH66336 in an in vivo murine model of Bcr/Abl-positive acute lymphoblastic leukemia. In the early leukemic phase, mice were randomly assigned to a treatment, a vehicle, and a nontreatment group. The treatment was well tolerated without any detectable side effects. All animals of the control groups died of leukemia/lymphoma within 103 days (range, 18-103 days). In contrast, 80% of the drug-receiving group survived without any signs of leukemia or lymphoma until termination of treatment, after a median treatment period of 200 days (range, 179-232 days). We conclude that farnesyl transferase inhibitor SCH66336 is able to revert early signs of leukemia and significantly prolongs survival in a murine ALL model.
Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to clinical scale from a single blood draw using dendritic cells and HLA-tetramers
Authors: Szmania Susann , Galloway Amanda , Bruorton Mary , Musk Philip , Aubert Geraldine , Arthur Andrew , Pyle Haywood , Hensel Nancy , Ta Nga , Lamb Lawrence , Dodi Toni , Madrigal Alejandro , Barrett John , Henslee-Downey Jean , van Rhee Frits
Published: July 2002

Cytomegalovirus (CMV) reactivation in immunocompromised recipients of allogeneic stem cell transplantation is a cause of morbidity and mortality from viral pneumonitis. Antiviral drugs given to reactivating patients have reduced the mortality from CMV but have toxic side effects and do not always prevent late CMV disease. Cellular immunotherapy to prevent CMV disease is less toxic and could provide prolonged protection. However, a practical approach to generating sufficient quantities of CMV-specific cytotoxic T cells (CTLs) is required. This study describes a system for generating sufficient CMV-specific CTLs for adoptive immunotherapy of HLA-A*0201 bone marrow transplant recipients from 200 mL donor blood. Donor monocytes are used to generate dendritic cells (DCs) in medium with autologous plasma, interleukin 4, granulocyte-macrophage colony-stimulating factor, and CD40 ligand. The DCs are pulsed with the immunodominant HLA-A*0201–restricted CMV peptide pp65495-503, and incubated with donor T cells. These cultures are restimulated twice with peptide-pulsed lymphoblastoid cell lines (LCLs) or CD40-ligated B cells and purified with phycoerythrin (PE)–labeled pp65495-503/HLA-A*0201 tetramers by flow sorting, or with anti-PE paramagnetic beads. The pure tetramer-positive population is then rapidly expanded to obtain sufficient cells for clinical immunotherapy. The expanded CTLs are more than 80% pure, of memory phenotype, with a Tc1 cytokine profile. They efficiently kill CMV-infected fibroblasts and express the integrin VLA-4, suggesting that the CTLs could cross endothelial barriers. This technique is reproducible and could be used for generating CMV-specific CTLs to prevent CMV disease after allogeneic blood and marrow transplantation.
Differential inhibition of adenosine diphosphate– versus thrombin receptor–activating peptide–stimulated platelet fibrinogen binding by abciximab due to different glycoprotein IIb/IIIa activation kinetics
Authors: Weber Artur-Aron , Schrör Karsten
Published: July 2002

The exposure of internal glycoprotein (GP) IIb/IIIa receptors has been proposed to explain the incomplete inhibition of aggregation of thrombin receptor–activating peptide (TRAP)-stimulated platelets by abciximab. However, a marked and rapid externalization of GPIIb/IIIa was also observed upon stimulation with 30 μM adenosine diphosphate (ADP). ADP-induced fibrinogen binding was completely inhibited by 10 μg/mL abciximab, 30 nM tirofiban, or 3 μg/mL eptifibatide, while fibrinogen binding induced by 100 μM TRAP was inhibited only by 50%. Interestingly, striking differences in fibrinogen binding kinetics in ADP- versus TRAP-stimulated platelets were observed. ADP-induced fibrinogen binding was much slower than that of abciximab. These differences in the fibrinogen binding rate were due to differential GPIIb/IIIa activation kinetics because the actual fibrinogen binding rate (measured by adding fibrinogen after platelet activation) was similar in ADP- and TRAP-stimulated platelets. Thus, the TRAP-induced GPIIb/IIIa activation rate would allow significant amounts of fibrinogen to occupy externalized GPIIb/IIIa receptors even in the presence of the inhibitor.
Adenovirus type 5 vectors induce dendritic cell differentiation in human CD14+ monocytes cultured under serum-free conditions
Authors: Lyakh Lyudmila A. , Koski Gary K. , Young Howard A. , Spence Sally E. , Cohen Peter A. , Rice Nancy R.
Published: July 2002

To determine whether infection by a model virus is capable of initiating dendritic cell (DC) differentiation, human CD14+peripheral blood monocytes were infected with replication-defective type 5 adenovirus. Under serum-free conditions, this resulted in differentiation of a majority of cells toward a DC phenotype within 36 to 48 hours, without the need for cytokine-induced predifferentiation. Infection induced DC morphology and altered the expression of surface markers, including loss of CD14, de novo induction of CD83 and CD25, and strongly augmented expression of CD86, CD80, CD40, and HLA-DR and HLA class I molecules. Differentiated cells maintained immunophenotype without loss of viability for at least 2 days after removal of the differentiation agent and cytokines. A greatly enhanced capacity to stimulate T-lymphocyte alloproliferation and increased expression of the DC-associated transcription factor RelB were observed. Virus without transgene was found to induce changes similar to transgene-expressing viruses. RelB up-regulation and DC immunophenotype were sensitive to the antioxidant N-acetylcysteine, suggesting a critical role for nuclear factor κB. RNAse protection assays revealed elevated levels of messenger RNA for a number of chemokines and cytokines associated with DCs. Finally, during differentiation, adenovirus-infected monocytes were shown to secrete chemokines and cytokines, including tumor necrosis factor-α (TNF-α). Furthermore, a TNF-α–neutralizing antibody inhibited the expression of some DC surface markers, indicating a contributing role for this cytokine in the adenovirus-induced differentiation of DC from monocytes. These findings have implications for the biology of monocytes as precursors to DCs and also for the use of recombinant adenovirus in vaccines or gene therapy.
Management of Patients With Chronic Coronary Disease
Authors: German Charles A. , Davis Andrew M. , Polonsky Tamar S.
Published: July 2024

This JAMA Clinical Guidelines Synopsis summarizes the 2023 American Heart Association (AHA)/American College of Cardiology (ACC) guideline on management of patients with chronic coronary disease.