bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal gating of CFTR requires ATP binding to both nucleotide-binding domains and hydrolysis at the second nucleotide-binding domain
Authors: Berger Allan L. , Ikuma Mutsuhiro , Welsh Michael J.
Published: December 2004

ATP interacts with the two nucleotide-binding domains (NBDs) of CFTR to control gating. However, it is unclear whether gating involves ATP binding alone, or also involves hydrolysis at each NBD. We introduced phenylalanine residues into nonconserved positions of each NBD Walker A motif to sterically prevent ATP binding. These mutations blocked [α-
32
P]8-N
3
-ATP labeling of the mutated NBD and reduced channel opening rate without changing burst duration. Introducing cysteine residues at these positions and modifying with
N
-ethylmaleimide produced the same gating behavior. These results indicate that normal gating requires ATP binding to both NBDs, but ATP interaction with one NBD is sufficient to support some activity. We also studied mutations of the conserved Walker A lysine residues (K464A and K1250A) that prevent hydrolysis. By combining substitutions that block ATP binding with Walker A lysine mutations, we could differentiate the role of ATP binding vs. hydrolysis at each NBD. The K1250A mutation prolonged burst duration; however, blocking ATP binding prevented the long bursts. These data indicate that ATP binding to NBD2 allowed channel opening and that closing was delayed in the absence of hydrolysis. The corresponding NBD1 mutations showed relatively little effect of preventing ATP hydrolysis but a large inhibition of blocking ATP binding. These data suggest that ATP binding to NBD1 is required for normal activity but that hydrolysis has little effect. Our results suggest that both NBDs contribute to channel gating, NBD1 binds ATP but supports little hydrolysis, and ATP binding and hydrolysis at NBD2 are key for normal gating.
Pax2 expression occurs in renal medullary epithelial cells
in vivo
and in cell culture, is osmoregulated, and promotes osmotic tolerance
Authors: Cai Qi , Dmitrieva Natalia I. , Ferraris Joan D. , Brooks Heddwen L. , van Balkom Bas W. M. , Burg Maurice
Published: December 2004

Pax2 is a transcription factor that is crucial for kidney development, and it is also expressed in the normal adult kidney, where its physiological function is unknown. In the present study, we find by cDNA microarray analysis that Pax2 expression in second-passage mouse inner-medullary epithelial cells is increased by a high NaCl concentration, which is significant because NaCl levels are normally high in the inner medulla
in vivo
, and varies with urinary concentration. Furthermore, a high NaCl concentration increases Pax2 mRNA and protein expression in mouse inner medullary collecting duct (mIMCD3) cells, and its transcriptional activity. Pax2 mRNA and protein expression is high in normal adult mouse renal inner medulla but much lower in renal cortex. Pax2 protein is present in collecting duct cells in both renal medulla and cortex and in thin descending limbs of Henle's loop in inner medulla. Treating Brattleboro rats with desamino-Cys-1,
d
-Arg-8 vasopressin, which increases inner-medullary NaCl concentration, causes a 4-fold increase in inner-medullary Pax2 protein. Treatment with furosemide, which decreases inner-medullary NaCl, reduces inner-medullary Pax2 mRNA and protein. Pax2-specific short interfering RNA increases high NaCl concentration-induced activation of caspase-3 and apoptotic bodies in mIMCD3 cells. We thus conclude that (
i
) Pax2 is expressed in normal renal medulla, (
ii
) its expression is regulated there by the normally high and variable NaCl concentration, and (
iii
) it protects renal medullary cells from high NaCl concentration-induced apoptosis.
Specialized membrane-localized chaperones prevent aggregation of polytopic proteins in the ER
Authors: Kota Jhansi , Ljungdahl Per O.
Published: December 2004

The integral endoplasmic reticulum (ER) membrane protein Shr3p is required for proper plasma membrane localization of amino acid permeases (AAPs) in yeast. In the absence of Shr3p AAPs are uniquely retained in the ER with each of their twelve membrane-spanning segments correctly inserted in the membrane. Here, we show that the membrane domain of Shr3p specifically prevents AAPs from aggregating, and thus, plays a critical role in assisting AAPs to fold and correctly attain tertiary structures required for ER exit. Also, we show that the integral ER proteins, Gsf2p, Pho86p, and Chs7p, function similarly to Shr3p. In cells individually lacking one of these components only their cognate substrates, hexose transporters, phosphate transporters, and chitin synthase-III, respectively, aggregate and consequently fail to exit the ER membrane. These findings indicate that polytopic membrane proteins depend on specialized membrane-localized chaperones to prevent inappropriate interactions between membrane-spanning segments as they insert and fold in the lipid bilayer of the ER membrane.
MITF links differentiation with cell cycle arrest in melanocytes by transcriptional activation of INK4A
Authors: Loercher Amy E. , Tank Elizabeth M.H. , Delston Rachel B. , Harbour J. William
Published: December 2004

Cell cycle exit is required for proper differentiation in most cells and is critical for normal development, tissue homeostasis, and tumor suppression. However, the mechanisms that link cell cycle exit with differentiation remain poorly understood. Here, we show that the master melanocyte differentiation factor, microphthalmia transcription factor (MITF), regulates cell cycle exit by activating the cell cycle inhibitor INK4A, a tumor suppressor that frequently is mutated in melanomas. MITF binds the INK4A promoter, activates p16Ink4a mRNA and protein expression, and induces retinoblastoma protein hypophosphorylation, thereby triggering cell cycle arrest. This activation of INK4A was required for efficient melanocyte differentiation. Interestingly, MITF was also required for maintaining INK4A expression in mature melanocytes, creating a selective pressure to escape growth inhibition by inactivating INK4A. These findings demonstrate that INK4A can be regulated by a differentiation factor, establish a mechanistic link between melanocyte differentiation and cell cycle exit, and potentially explain the tissue-specific tendency for INK4A mutations to occur in melanoma.
Coupling of Voltage Sensing to Channel Opening Reflects Intrasubunit Interactions in Kv Channels
Authors: Labro Alain J. , Raes Adam L. , Snyders Dirk J.
Published: December 2004

Voltage-gated K+ channels play a central role in the modulation of excitability. In these channels, the voltage-dependent movement of the voltage sensor (primarily S4) is coupled to the (S6) gate that opens the permeation pathway. Because of the tetrameric structure, such coupling could occur within each subunit or between adjacent subunits. To discriminate between these possibilities, we analyzed various combinations of a S4 mutation (R401N) and a S6 mutation (P511G) in hKv1.5, incorporated into tandem constructs to constrain subunit stoichiometry. R401N shifted the voltage dependence of activation to negative potentials while P511G did the opposite. When both mutations were introduced in the same α-subunit of the tandem, the positive shift of P511G was compensated by the negative shift of R401N. With each mutation in a separate subunit of a tandem, this compensation did not occur. This suggests that for Kv channels, the coupling between voltage sensing and gating reflects primarily an intrasubunit interaction.
The Cooperative Voltage Sensor Motion that Gates a Potassium Channel
Authors: Pathak Medha , Kurtz Lisa , Tombola Francesco , Isacoff Ehud
Published: December 2004

The four arginine-rich S4 helices of a voltage-gated channel move outward through the membrane in response to depolarization, opening and closing gates to generate a transient ionic current. Coupling of voltage sensing to gating was originally thought to operate with the S4s moving independently from an inward/resting to an outward/activated conformation, so that when all four S4s are activated, the gates are driven to open or closed. However, S4 has also been found to influence the cooperative opening step (Smith-Maxwell et al., 1998a), suggesting a more complex mechanism of coupling. Using fluorescence to monitor structural rearrangements in a Shaker channel mutant, the ILT channel (Ledwell and Aldrich, 1999), that energetically isolates the steps of activation from the cooperative opening step, we find that opening is accompanied by a previously unknown and cooperative movement of S4. This gating motion of S4 appears to be coupled to the internal S6 gate and to two forms of slow inactivation. Our results suggest that S4 plays a direct role in gating. While large transmembrane rearrangements of S4 may be required to unlock the gating machinery, as proposed before, it appears to be the gating motion of S4 that drives the gates to open and close.
Mismatch: Historical Perspectives on Schools and Students who Don't Fit Them
Authors: Deschenes Sarah , Cuban Larry , Tyack David
Published: December 2004

There have always been students who do not meet the educational expectations of their time—students outside the mainstream mold who do not fit dominant notions of success. The differences between schools and these students can be thought of as a “mismatch” between the structure of schools and the social, cultural, or economic backgrounds of students identified as problems. In this essay we examine the history of these students who have not been able to do what educators wanted them to do. We look at how educators have labeled poor school performers in different periods and how these labels reflected both attitudes and institutional conditions. We then summarize four major historical explanations for why children fail in school—individual deficits or incompetence, families, inefficiency in schools, and cultural difference. Finally, we explore what implications this history has for students in the current standards-based reform movement, including implications for social promotion and the age-graded school. To avoid a mismatch in the standards movement, we argue that educators should focus on adapting the school better to the child, addressing social inequalities that extend beyond the classroom, and undertaking comprehensive changes that take no features of current schools for granted.
Constructing Failure, Narrating Success: Rethinking the “Problem” of Teen Pregnancy
Authors: Schultz Katherine
Published: December 2004

In this article I argue that either the anticipation or the reality of pregnancy and motherhood shaped young women's participation in their senior year in a multiracial urban high school. In my interviews and analyses of public writing and classroom talk, I discovered frequent references to motherhood as young women made ambitious plans for their futures at the same time they worried about children. The article contrasts the discourses of adolescent pregnancy in the mainstream press to the narratives of low-income young women of color in my study. There is a paradox in the narratives I collected: Females without children claimed they could only succeed if they managed to avoid becoming pregnant. Young mothers in the same peer group explained their success or persistence in school as due, in part, to their children. These stories belie simple explanations of the success or failure of females of color living in poverty. The media contentions that these youth don't care, that they have resorted to drugs, babies, and dropping out, fail to acknowledge the complexity of the identities of adolescents living in poverty. In their lives, these young women are actively turning others’ constructions of them as failures into their own narratives of success. I suggest that educators and policy makers use students’ conceptions of the role that pregnancy and motherhood play in their school careers and futures to rethink the “problem” of teen pregnancy and to reimagine and redefine the opportunity structures available for young women in high school and beyond.
Redefining “Public” Education: Charter Schools, Common Schools, and the Rhetoric of Reform
Authors: Lubienski Chris
Published: December 2004

Virtually every definition of charter schools asserts that they are a form of public schooling. This article poses the question: In what way? Charter school advocates, observers, and opponents all note that the schools are publicly funded, are open to all, and are chartered by public entities. This analysis pursues the question by comparing the rhetoric regarding the definition of public education employed by charter school reformers in one state, Michigan, with that of the common school reformers of the 19th century, particularly Horace Mann. The analysis finds conflicting definitions of what constitutes public schooling. Although both reforms support tax-funded schools and open access, the common school reformers emphasized political-democratic forms of control. Charter school advocates actively challenge such control, and elevate market mechanisms of consumer choice and competition between providers as the primary means of authority. To advance such a program, proponents of charter schools explicitly seek to “redefine” popular conceptions of what constitutes public and private education. In doing so, they frame education principally as a consumer good, and, this article theorizes, effect a privatization of the purpose of public education that contrasts with the common school reformers’ stated concern for democracy and the public good.
Dewey and Peirce, the Philosopher's Philosopher
Authors: Prawat Richard S.
Published: December 2004

Three arguments are presented in this article that point to discontinuity rather than continuity in John Dewey's philosophical views. First, the author examines and critiques the most comprehensive current account of the development of Dewey's thinking early to late based on the assumption of continuity. Contrary to this account, it is argued, Dewey dramatically changed his views about the role of action, language, and quality in knowledge construction from mid-career on. In the second and third sections of the paper, numerous examples are presented showing how closely Dewey's later ideas map onto those of the brilliant but less known originator of pragmatism, Charles Sanders Peirce. The intent in all three sections of the paper is to demonstrate the magnitude of Dewey's debt to Peirce.
Staff members’ feelings toward psychiatric patients related to their own and the patient's self‐image and gender
Authors: Armelius Kerstin , Holmqvist Rolf
Published: December 2004

The relation between staff members’ feelings toward a patient and their own and the patient's self‐image in different gender combination groups was studied. Staff at 16 psychiatric treatment homes for patients with severe psychopathology reported their feelings toward their patients on a number of occasions. At the start of treatment, both staff members and patients rated their self‐images using the Structural Analysis of Social Behavior (SASB). Male staff seemed less influenced by the patient, with their feelings relating mainly to aspects of their own self‐image, while the feelings of the female staff were more related to the patient's self‐image. The patient's diagnosis was less important for a staff member's feelings than that member's self‐image. Generally, the relation between feelings and self‐image was stronger for negative feelings. The results point to the importance of understanding more about the influence of staff members’ self‐structure on their negative feelings toward their patients and how this relates to both the staff member's and patient's gender.
Pharmacological and physiological aspects of sexual exhaustion in male rats
Authors: Fernández‐Guasti Alonso , Rodríguez‐Manzo Gabriela
Published: December 2004

The present article reviews the current findings on the interesting phenomenon of sexual satiety. Knut Larsson in 1956 reported on the development of sexual exhaustion in the male rat after repeated copulation. We have studied the process and found the following results. (1) One day after 4 hours of ad libitum copulation, two‐thirds of the population showed complete inhibition of sexual behavior, while the other third displayed a single ejaculatory series from which they did not recover. (2) Several pharmacological treatments, including 8‐OH‐DPAT, yohimbine, naloxone and naltrexone, reverse this sexual satiety, indicating that the noradrenergic, serotonergic and opiate systems are involved in this process. Indeed, direct neurochemical determinations showed changes in various neurotransmitters during sexual exhaustion. (3) Given enough stimulation, by changing the stimulus female, sexual satiety was prevented, suggesting that there are motivational components of the sexual inhibition that characterizes sexual exhaustion. (4) The GABA antagonist bicuculline, or the electrical stimulation of the medial preoptic area, did not reverse sexual exhaustion. These data suggest, on the one hand, that sexual exhaustion and the postejaculatory interval (which is shortened by bicuculline administration) are not mediated by similar mechanisms and, on the other, that the medial preoptic area does not regulate sexual satiety. (5) The androgen receptor density in brain areas closely related to the expression of masculine sexual behavior, such as the medial preoptic nucleus, was drastically reduced in sexually exhausted animals. Such reduction was specific to certain brain areas and was not related to changes in the levels of androgens. These results suggest that changes in brain androgen receptors account for the inhibition of sexual behavior present during sexual exhaustion. (6) The recovery process of sexual satiety after 4 hours of ad libitum copulation reveals that, after 4 days, only 63% of the males are able to show sexual behavior while after 7 days all animals display copulatory activity.
Participation and Social Capital Formation: Norway in a Comparative Perspective1
Authors: Wollebæk Dag , Selle Per
Published: December 2004

Voluntary associations are often ascribed a fundamental role in the formation of social capital. However, scholars disagree on the extent to which face‐to‐face contact, i.e. active participation, is necessary to create this resource. The impact of participation in associations on social capital is examined using three dimensions: intensity (active vs. passive participation), scope (many vs. few affiliations) and type (non‐political vs. political purpose). While those affiliated display higher levels of social capital than outsiders, the difference between active and passive members is absent or negligible. The only cumulative effect of participation occurs when the member belongs to several associations simultaneously, preferably ones with different purposes.
Transition in a Cold Climate: Management Regimes and Rural Marginalisation in Northwest Russia
Authors: Eikeland Sveinung , Riabova Larissa
Published: December 2004

This paper examines why and how the development of the forestry and fishery sectors in Northwest Russia have taken very different trajectories during the transition period and examines the impacts of these trajectories on the rural areas concerned. The drive to establish natural resources as “resources” in an economic sense during the transition period acts as the starting point for the analysis. However, the success of this drive has depended on the adaptation of formerly Soviet institutions to the new circumstances. These include the privatisation of Soviet production units (lespromkhozes and fishery kolkhozes) and the introduction of new systems for the distribution of fish and forest resources (auctions and quotas). From the analysis of data collected from four types of actors in Murmansk Oblast (a collective fishing farm, State owned logging companies in forestry villages, fishery management units and local forest management structures), the paper seeks to present these actors’ adaptations, changes, opportunities and ultimately destiny during the 1990s.
The Syntactic Disguises of the Predication Operator
Authors: Eide Kristin M. , Åfarli Tor A.
Published: December 2004

Taking Bowers (1993) as our point of departure, we argue that natural language employs a predication operator that may be lexicalised and constitute the head of a syntactic projection. First, following Bowers' suggestion that the English particle as may lexicalise the predication operator, we show that the corresponding particle som of certain clauses in Norwegian serves the same function. Then, departing from Bowers, we argue that the copula and certain prepositions may lexicalise the predication operator as well. Last, we argue against Bowers' non‐unitary construal of the verb phrase as made up of a V‐projection and an independent predication projection. Instead, we adduce evidence that the predication operator is directly lexicalised by the main verb, in effect claiming that the unmarked verb phrase is a unitary VP, with V′ constituting a Fregean unsaturated function exactly in virtue of having the predication operator incorporated into the main verb.
Formally–grounded phonology: From constraint–based theories to theory–based constraints
Authors: De Carvalho Joaquim Brandão
Published: December 2004

It is argued here that most phonological theory is not theoretical, but based on primitives and axioms (the so–called ‘constraints’) which derive directly from the data they are supposed to explain. This article attempts to show what a non–circular conception of phonological theory may look like. The number of segmental primes, their markedness value, phonological content, and combinatory properties, as well as currently assumed constraints on syllable structure are shown to follow from a Boolean algebra, and, thus, to be independently motivated theory–grounded theorems. Hence, for example, neither the ONSET nor the NO–CODA constraints posited by OT are required. Another issue of the present theory is that segmental content and syllable structure and interdependent aspects, which emerge from the determination of skeletal units.
Determiners and word order in Scandinavian DPs
Authors: Julien Marit
Published: December 2004

This article deals with the distribution of prenominal and suffixed determiners/articles in Scandinavian DPs, and with the overall order of constituents inside the DP. Following Longobardi (2001), I argue that although Scandinavian allows the D projection to be empty under certain conditions, the D projection must be visible at PF when the reference of the DP as a whole depends on D. In such cases, either D itself is spelled out, or else a constituent agreeing with D is moved to Spec DP. The Scandinavian varieties make use of different strategies in this respect, and the result is considerable variation in the shape of the DP.
Flow Past a Swept Wing with a Compliant Surface: Stabilizing the Attachment‐Line Boundary Layer
Authors: Allen Leanne , Bridges Thomas J.
Published: December 2004

Many aquatic species such as dolphins and whales have fins, which can be modeled as swept wings. Some of these fins, such as the dorsal fin of a dolphin, are semi‐rigid and therefore can be modeled as a rigid swept wing with a compliant surface. An understanding of the hydrodynamics of the flow past swept compliant surfaces is of great interest for understanding potential drag reduction mechanisms, especially since swept wings are widely used in hydrodynamic and aerodynamic design. In this paper, the flow past a swept wing with a compliant surface is modeled by an attachment‐line boundary layer flow, which is an exact similarity solution of the Navier–Stokes equations, flowing past a compliant surface modeled as an elastic plate. The hydrodynamic stability of the coupled problem is studied using a new numerical framework based on exterior algebra. The basic instability of the attachment line boundary layer on a rigid surface is a traveling wave instability that propagates along the attachment line, and numerical results show that the compliance results in a substantial reduction in the instability region. Moreover, the results show that, although the flow‐field is three‐dimensional, the qualitative nature of the instability suppression is very similar to the qualitative reduction of instability of the two‐dimensional Tollmien–Schlichting modes in the classical boundary‐layer flow past a compliant surface.
Geometrical Optics and Models of Computer Memory Fragmentation
Authors: Knessl Charles
Published: December 2004

We analyze a two‐dimensional difference equation that arose in a stochastic model of memory fragmentation in computers. We use the ray method of geometrical optics, and other singular perturbation methods, to solve this equation asymptotically. The asymptotic limit corresponds to one of heavy system usages. We interpret the results from the ray method probabilistically.
Networking for Teacher Learning: Toward a Theory of Effective Design
Authors: Mcdonald Joseph P. , Klein Emily J.
Published: December 2004

This article focuses on one theory of school reform that seeks to counteract insularity among teachers with respect to questions of what to teach and how. It networks teachers across schools and gives them access to outside expertise in their content areas. In this approach teacher learning happens within a series of face-to-face and virtual meetings, sometimes over many years. In this article, we focus on teacher networking and, more specifically, on how teacher networks design for teacher learning. By describing several dynamic tensions inherent in the designs of a sample of teacher networks, and by raising questions about these tensions and their relation to teacher learning, we hope to contribute toward the building of a theory of effective network design. We illustrate these design concepts with references to the work of seven networks that aim to revamp teachers’ knowledge in the humanities. In the final section of the article, we offer several sets of questions that derive from our analysis and that might form the basis for further research.
The Weakest Link
Authors: Fletcher Mike , Mooney Claire
Published: December 2004

This article discusses optimal strategies for contestants in a well‐known television game show.
Record Values and Surviving Glacial Moraines
Authors: Johnson Roger
Published: December 2004

Estimating the number of glacial advances from surviving glacial debris can, amazingly enough, be cast as a records problem for which there is a substantial statistical literature. As a result, instructors may illustrate method of moments and maximum‐likelihood estimation techniques with an interesting problem in the physical sciences.
Do Football Teams Have Clusters of Wins, Draws and Defeats?
Authors: Smeeton Nigel
Published: December 2004

The issue of whether football teams have good or bad patches during the course of a season is of concern to many supporters. This interest can be harnessed to make the classroom teaching of probability more relevant. In this article, the unfamiliar runs test for multiple outcomes is used to test for possible clustering in wins, draws and defeats in a short series of consecutive matches.
Exploring the Probabilities of ‘Who Wants to be a Millionaire?’
Authors: Quinn Robert J.
Published: December 2004

This article discusses three probabilistic scenarios based on the television game show ‘Who Wants to be a Millionaire?’. These situations provide motivational opportunities for high‐school students to explore the concepts of expected value, permutations and independent events.
India and the Impossible Trinity
Authors: Joshi Vijay
Published: December 2004

In the 1990s, India responded to the well‐known trilemma of macroeconomic policy by adopting an intermediate exchange rate system combined with selective capital controls. This regime enabled the country to balance exchange rate stability, exchange rate targeting and monetary autonomy, and to weather successfully various shocks that included contagion from the East Asian crisis. India's experience serves to reinforce doubts about the desirability of bipolar exchange rate regimes for developing countries as an integral element of a new international financial architecture.
Markov Random-Field Models for Estimating Local Labour Markets
Authors: Sebastiani Maria Rita
Published: December 2004

This work is motivated by data on daily travel-to-work flows observed between pairs of elemental territorial units of an Italian region. The data were collected during the 1991 population census. The aim of the analysis is to partition the region into local labour markets. We present a new method for this which is inspired by the Bayesian texture segmentation approach. We introduce a novel Markov random-field model for the distribution of the variables that label the local labour markets for each territorial unit. Inference is performed by means of Markov chain Monte Carlo methods. The issue of model hyperparameter estimation is also addressed. We compare the results with those obtained by applying a classical method. The methodology can be applied with minor modifications to other data sets.
Immunochemical detection of prion protein on dipsticks prepared with crystalline bacterial cell‐surface layers
Authors: Völkel Dirk , Zimmermann Klaus , Breitwieser Andreas , Pable Sabrina , Glatzel Markus , Scheiflinger Friedrich , Schwarz Hans P. , Sara Margit , Sleytr Uwe B. , Dorner Friedrich
Published: December 2004

BACKGROUND: Transmissible spongiform encephalopathy (TSE) represents a spectrum of diseases affecting humans and animals. A definitive diagnosis of TSEs is only possible by postmortem identification of pathologic prion protein in brain tissue that has been treated with protease. The pathologic protein is detected by Western blot analysis or ELISA methods. The bovine spongiform encephalopathy crisis and occurrence of a new variant of CJD has increased demand for rapid and simple assays.

STUDY DESIGN AND METHODS: A dipstick assay has been developed for prion diagnosis based on a sandwich ELISA specific for prion protein, and crystalline bacterial cell‐surface layers (S‐layers) were used as an immo‐bilization matrix. The usefulness of the dipstick assay was evaluated by determining the detection limit, comparison with other methods, and analysis of CJD samples.

RESULTS: The sensitivity of the prion dipsticks was similar to that published for time‐resolved fluorescence ELISA methods. After protease treatment, pathologic prion protein could be detected specifically.

CONCLUSION: The dipstick assay is a sensitive and specific test useful for the detection of prion protein. The simplicity of the S‐layer dipstick lends itself to a variety of potential applications including field diagnostics.
Clinical evaluation of an HIV‐1 and HCV assay and demonstration of significant reduction of the HCV detection window before seroconversion
Authors: Katsoulidou Antigoni S. , Moschidis Zissis M. , Gialeraki Renia E. , Paraskevis Dimitrios N. , Sypsa Vana A. , Lazanas Marios C. , Tassopoulos Nicholaos C. , Psichogiou Mina A. , Boletis John N. , Karafoulidou Anastasia S. , Hatzakis Angelos E.
Published: December 2004

BACKGROUND:  One HIV‐1 and HCV assay simultaneously detects HIV‐1 and HCV RNA (Procleix, Chiron Corp.). The main intended use of the assay is the testing of blood and blood products in blood banking.

STUDY DESIGN AND METHODS:  To evaluate the clinical sensitivity of the assay, 164 anti‐HIV‐1+ and 160 anti‐HCV+ patients of different viral load were tested. The assay specificity was determined in 1000 HIV‐1‐ and HCV‐seronegative blood donors. The ability of the assay to detect different HCV genotypes was investigated in a total of 40 patients of different genotypes (1‐4). Furthermore, to investigate the reduction of the HCV window phase before seroconversion, serial samples of 25 hemodialysis patients who seroconverted to anti‐HCV were also tested.

RESULTS:  The assay detected all 60 HIV‐1‐infected patients with a viral load of greater than 50 copies per mL and 48 of 104 patients with a viral load of less than 50 copies per mL. Moreover, all 60 patients with an HCV RNA load of greater than 521 IU per mL and 7 of 100 patients with a viral load of less than 50 IU per mL tested positive. The assay specificity was found to be 100 percent. In addition, all 40 patients of different HCV genotypes were successfully detected. Finally, the median time that the assay detected HCV infection before second‐ and third‐generation anti‐HCV assay was found to be 183 and 91 days, respectively.

CONCLUSION:  The assay sensitivity and specificity, its ability to detect different HCV genotypes, and the significant reduction of window period of HCV infection further support its use for improving the safety of blood and blood products.
A comparison of PLT collections from two apheresis devices
Authors: Bueno José Luis , Barea Luisa , García Fernando , Castro Emma
Published: December 2004

BACKGROUND:  The aim of this study was to compare two apheresis devices (COBE Trima and COBE Spectra, Gambro BCT).

STUDY DESIGN AND METHODS:  The study compares 103 Trima procedures with 61 Spectra procedures. The comparison of single‐donor PLTs (SDPs) separation parameters and anticoagulant infusion to the donors were the primary targets. Yield and residual amounts of WBCs of SDPs were secondary targets. Residual amounts of WBCs were measured with the Nageotte method.

RESULTS:  Trima and Spectra groups were comparable before apheresis. Two procedures were terminated before completion in the Trima group owing to vein damage. Trima infused more anticoagulant—352 ± 104 mL versus 297 ± 75 mL (p < 0.01)—and was quicker than Spectra. The time to obtain 3.5 × 1011 was (median) 55.8 minutes for the Trima machine and 80.3 minutes for Spectra machine (p < 0.001). Regarding leukoreduction, all the SDPs had fewer than 1 × 106 WBCs per unit except for one in product obtained by the Trima machine.

CONCLUSIONS:  The Trima machine is faster and more efficient than the Spectra machine, and both machines allow standard leukoreduced SDPs to be obtained. Although donors receive a higher anticoagulant infusion with the Trima machine, their tolerance is acceptable.
Immune hemolytic anemia associated with teicoplanin
Authors: Coluccio Elena , Villa M. Antonietta , Villa Emmanuel , Morelati Fernanda , Revelli Nicoletta , Paccapelo Cinzia , Garratty George , Rebulla Paolo
Published: December 2004

BACKGROUND:  Several drugs can cause immune hemolytic anemia. Here a patient who developed hemolytic anemia after treatment with teicoplanin is described.

CASE REPORT:  Owing to a two‐vessel disease, a 68‐year‐old white man underwent coronary artery bypass grafting. He was readmitted for superficial sternal wound infection and sternal instability. Rewiring was required and worsening anemia characterized the course after the reoperation. Drugs used in the second admission were gentamycin, teicoplanin, paracetamol, and codeine. They were considered as a possible cause of drug‐induced hemolytic anemia.

RESULTS:  The DAT was positive for complement and IgG. Autoanti‐e was identified in the patient's undiluted serum sample. The eluate was reactive with all RBCs tested only after adding teicoplanin; when diluted 1:4, anti‐e specificity was observed in the presence of teicoplanin.

CONCLUSION:  To our knowledge, this is the first report of immune hemolytic anemia owing to teicoplanin.
Are catch‐up reefs an artefact of coring?
Authors: Blanchon Paul , Blakeway David
Published: December 2004

Drill cores through modern coral reefs commonly show a time lag in reef initiation followed by a phase of rapid accretion to sea level from submerged foundations – the so‐called ‘catch‐up response’. But because of the difficulty of drilling in these environments, core distribution is usually restricted to accessible areas that may not fully represent reef history, especially if the reef initiated in patches or developed with a prograde or retrograde geometry. As a consequence, core data have the potential to give a misleading impression of reef development, particularly with respect to the timing of initiation and response to sea‐level rise. Here, we use computer models to simulate keep‐up reef development and, from them, quantify variations in the timing of reef initiation and accretion rate using mock cores taken through the completed simulations. The results demonstrate that cores consistently underestimate the timing of reef initiation and overestimate the reef accretion rate so that, statistically, a core through a keep‐up reef will most likely produce a catch‐up pattern – an initiation lag followed by a phase of rapid accretion to sea level. This implies that catch‐up signatures may be an artefact of coring and that keep‐up reefs are significantly more common than previous core studies claim.
The role of tectonism in sequence development and facies distribution of Upper Oligocene cool‐water carbonates: Coromandel Peninsula, New Zealand
Authors: Dix George R. , Nelson Campbell S.
Published: December 2004

The Torehina Formation is part of a cool‐water carbonate succession of Oligocene age in New Zealand that crops out on the Coromandel Peninsula, North Island. It contains two major transgressive sequences that record successive onlap of a once emergent landmass. The first sequence records marine flooding of non‐marine to marginal marine fan delta/estuarine facies, followed by deepening upward and formation of a low‐energy, deep (100+ m) muddy carbonate ramp. The capping sequence boundary is characterized by differential uplift and varies considerably in its character over a small (9 km2) area, varying from a burrowed glauconitic firmground to an erosional hardground to an undulatory marine contact to a palaeokarst with < 25 m relief. Sequence 2 sediments, which overlie the palaeokarst with minor (< 10°) angular unconformity, are clayey, marine (offshore) siltstones, whereas open‐marine limestones of equivalent age overlie the other boundary types with no apparent angular discordance. The siliciclastics could either represent lowstand channel deposits or may define interbank deposits contemporary with adjacent carbonates. Palaeogeographic restriction of palaeokarst and sequence 2 siliciclastics identifies a structural corridor oriented strike‐parallel to the adjacent Harauki Graben, which began to develop by this time. Palaeogeographical differences in the character of the basal limestone facies of sequence 2 also occur. These differences identify variation in accommodation during initial stages of deposition imposed by previous differential movement of fault blocks. As a result, relatively warm‐water (20 °C) Amphistegina‐bearing limestones in one area contrast with co‐existing deeper water, silty foraminiferal (benthic > planktic), echinoderm and bivalve limestones in another. This variation disappears upsection, which suggests that initial bathymetric differences were eliminated with renewed rise in sea level, yielding deeper water inner‐shelf sediment facies followed by the accumulation of still deeper, but higher energy, outer‐shelf bivalve and bryozoan facies. The sequence architecture of the Torehina Formation is controlled by tectonism, both long‐term subsidence and short‐term differential uplift. This arose as a result of increasing tectonic activity throughout proto‐New Zealand during the Late Oligocene. In such a system, local and regional variation in tectonism among adjacent basins can impose subtle to marked differences in the timing of sequence boundaries and the character of basin‐fill patterns.
A Theoretical Framework for Core Material Properties Identification in Cellular Solids using Novelty Detection
Authors: Scarpa F. , Manson G. , Ruzzene M.
Published: December 2004

Abstract:  This paper presents a novelty detection‐based technique to identify core material properties of honeycombs and cellular structures. A numerical model (finite element) representing full scale and/or reduced size of the cellular solid is used to generate transmissibilities between topological homologous points at cells in different locations. In order to make the procedure robust against noise, these transmissibilities are artificially corrupted. This step is representative of a series of experimentally obtained measurements which automatically return information relating to the size and shape of data noise along with the mean measurement. The next stage, both in this paper and in the proposal for the experimental approach, is to generate several further sets of transmissibilities from the finite element model; the only difference being that the core material properties are altered from the original values. A novelty detection framework is then adopted to find a similarity measure between each of these ‘test’ transmissibilities and the original set thereby identifying the material properties. Although this work is concerned with identifying only one material property, the methodology extends to identifying several properties.
Membrane Traffic in Skeletal Muscle
Authors: Towler Mhairi C. , Kaufman Stephen J. , Brodsky Frances M.
Published: December 2004

Skeletal muscle tissue is made up of highly organized multinuclear cells. The internal organization of the muscle cell is dictated by the necessary regular arrangement of repeated units within the protein myofibrils that mediate muscle contraction. Skeletal muscle cells have the usual membrane traffic pathways for partitioning newly synthesized proteins, internalizing cell surface receptors for hormones and nutrients, and mediating membrane repair. However, in muscle, these pathways must be further specialized to deal with targeting to and organizing muscle‐specific membrane structures, satisfying the unique metabolic requirements of muscle and meeting the high demand for membrane repair in a tissue that is constantly under mechanical stress. Specialized membrane traffic pathways in muscle also play a role in the formation of muscle through fusion of myoblast membranes and the development of internal muscle‐specific membrane structures during myogenesis and regeneration. It has recently become apparent that muscle‐specific isoforms of proteins that are known to mediate ubiquitous membrane traffic pathways, as well as novel muscle‐specific proteins, are involved in tissue‐specific aspects of muscle membrane traffic. Here we describe the specialized membrane structures of skeletal muscle, how these are developed, maintained and repaired by specialized and generic membrane traffic pathways, and how defects in these pathways result in muscle disease.
γ‐COP Appendage Domain – Structure and Function
Authors: Watson Peter J. , Frigerio Gabriella , Collins Brett M. , Duden Rainer , Owen David J.
Published: December 2004

COPI‐coated vesicles mediate retrograde transport from the Golgi back to the ER and intra‐Golgi transport. The cytosolic precursor of the COPI coat, the heptameric coatomer complex, can be thought of as composed of two subcomplexes. The first consists of the β‐, γ‐, δ‐ and ζ‐COP subunits which are distantly homologous to AP clathrin adaptor subunits. The second consists of the α‐, β′‐ and ε‐COP subunits. Here, we present the structure of the appendage domain of γ‐COP and show that it has a similar overall fold as the α‐appendage of AP2. Again, like the α‐appendage the γ‐COP appendage possesses a single protein/protein interaction site on its platform subdomain. We show that in yeast this site binds to the ARFGAP Glo3p, and in mammalian γ‐COP this site binds to a Glo3p orthologue, ARFGAP2. On the basis of mutations in the yeast homologue of γ‐COP, Sec21p, a second binding site is proposed to exist on the γ‐COP appendage that interacts with the α,β′,ε COPI subcomplex.
Ultrasonographic findings in abdominal mast cell disease: a retrospective study of 19 patients
Authors: Sato Amy F. , Solano Mauricio
Published: December 2004

A retrospective survey from January 1989 to January 1999 of Tufts University Foster Hospital for Small Animals radiology records of 12 dogs and seven cats with cytologically or histopathologically confirmed abdominal mast cell disease was performed. Ultrasound changes in hepatic mast cell infiltration in dogs included a subjective increase in size, a diffuse increase in echogenicity, and one or more hypoechoic nodules. Ultrasound findings in the affected canine spleen included one or more hypoechoic nodules and a subjective increase in size. Two ultrasonographically unremarkable canine livers and one unremarkable spleen were found to be infiltrated by mast cells. The mast cell‐infiltrated feline spleen was subjectively increased in size, mottled, irregular, or contained nodules. The affected lymph nodes in both dogs and cats were hypoechoic or inhomogeneous, subjectively increased in size, and rounded. Gastrointestinal involvement in cats was characterized by a thickened ileocecocolic junction or colon with loss of wall layering. Mast cells were not found in the gastrointestinal tract in any dog. One dog with mast cell infiltrate of the kidneys had multiple hypoechoic nodules in the cortex that distorted the outer contour of the kidney. Although these findings are not specific to the disease in either species, abdominal ultrasound is considered a useful tool for determining the extent of disease in small‐animal patients with mast cell tumor if used in conjunction with histopathology or cytology.
Hypofractionated radiation therapy of oral melanoma in five cats
Authors: Farrelly John , Denman David L. , Hohenhaus Ann E. , Patnaik Amiya K. , Bergman Philip J.
Published: December 2004

Five cats with melanoma involving the oral cavity were treated with hypofractionated radiation therapy (RT). Cobalt photons were used to administer three fractions of 8.0 Gray (Gy) for a total dose of 24 Gy. Four cats received radiation on days 0, 7, and 21 and one cat received radiation on days 0, 7, and 13. One of the cats received additional irradiation following the initial treatment course. Two cats received chemotherapy. Their age ranged from 11 to 15 years with a median age of 12 years. Three cats had a response to radiation, including one complete response and two partial responses. All five cats were euthanized due to progression of disease, with one cat having evidence of metastatic disease at the time of euthanasia. The median survival time for the five cats was 146 days (range 66–224 days) from the start of RT. The results of this study suggest that oral melanoma in cats may be responsive to hypofractionated RT, but response does not seem to be durable.
NEURONAL DYNAMICS UNDER PERIODIC STIMULI
Authors: GOPALSAMY K. , MOHAMAD S.
Published: December 2004

The convergence characteristics of a single dissipative Hopfield-type neuron with self-interaction under periodic external stimuli are considered. Sufficient conditions are established for associative encoding and recall of the periodic patterns associated with the external stimuli. Both continuous-time-continuous-state and discrete-time-continuous-state models are discussed. It is shown that when the neuronal gain is dominated by the neuronal dissipation on average, associative recall of the encoded temporal pattern is guaranteed and this is achieved by the global asymptotic stability of the encoded pattern.
Glass‐ceramics in the scheme of inorganic materials
Authors: Partridge Graham
Published: December 2004

Inorganic Materials I. Glasses, ceramics, and glass‐ceramics are examined in the first article of a regular series by Graham Partridge of GEC ALSTHOM. Their definitions, and their mechanical, electrical and thermal properties are summarized and the scene set for future articles.
Disorder in Charge Transport in doped polymers
Authors: Van der Auweraer Mark , De Schryver Frans C. , Borsenberger Paul M. , Bässler Heinz
Published: December 2004

Charge transport in molecular doped polymers has important applications in xerography, as well as being a theoretical challenge. Its investigation by determination of transient photocurrents is reviewed, with experiments and pertinent theories, such as hopping in a Gaussian density of states and the small polaron model, being outlined. The temporal features of the photocurrents, the field and temperature dependence of the charge carrier mobilities, and the influence of molecular properties—and what can be inferred from these—are discussed.