bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors among handgun retailers for frequent and disproportionate sales of guns used in violent and firearm related crimes
Authors: Wintemute G J , Cook P J , Wright M A
Published: December 2005

Objective:To determine the retailer and community level factors associated with frequent and disproportionate sales of handguns that are later used in violent and firearm related crimes (VFC handguns).

Design:Cross sectional. The authors used California records to identify all handguns sold by study subjects during 1996–2000 and federal gun tracing records to determine which of these guns had been recovered by a police agency in the US or elsewhere and traced by 30 September 2003.

Subjects and setting:The 421 licensed gun retailers in California selling at least 100 handguns annually during 1996–2000.

Main outcome measure:The number of VFC handguns per 1000 gun years of exposure. Differences are expressed as incidence rate ratios (RR) with 95% confidence intervals (CI).

Results:Subjects accounted for 11.7% of California retailers with handgun sales, 81.5% of handgun sales, and 85.5% of VFC handguns. Among subjects, the 3426 VFC handguns accounted for 48.0% of all traced handguns and 65.0% of those linked to a specified crime. The median VFC handgun trace rate was 0.5/1000 gun years (range 0–8.8). In multivariate analysis, this rate increased substantially for each single-point increase in the percentage of proposed sales that were denied because the purchasers were prohibited from owning guns (RR 1.43; 95% CI 1.32 to 1.56), and was increased for pawnbrokers (RR 1.26; 95% CI 1.02 to 1.55). Community level crime rates and sociodemographics had little predictive value.

Conclusions:Risk factors, largely determined at the retailer level, exist for frequent and disproportionate sales of handguns that are later used in violent and firearm related crimes. Screening to identify high risk retailers could be undertaken with data that are already available.
SEMI-LOSSLESS TEXT COMPRESSION
Authors: KAUFMAN YAIR , KLEIN SHMUEL T.
Published: December 2005

A new notion, that of semi-lossless text compression, is introduced, and its applicability in various settings is investigated. First results suggest that it might be hard to exploit the additional redundancy of English texts, but the new methods could be useful in applications where the correct spelling is not important, such as in short emails, and the new notion raises some interesting research problems in several different areas of Computer Science.
ARITHMETIC CODING IN PARALLEL
Authors: ŠUPOL JAN , MELICHAR BOŘIVOJ
Published: December 2005

We present an EREW PRAM cost optimal parallel algorithm for arithmetic coding computation. We solve the problem in [Formula: see text] time using n/log n processors. Each part of the algorithm as well as a well-known parallel prefix computation forming a basis of the algorithm are clarified on simple examples.
INCREMENTAL DESIGN METHODOLOGY FOR MULTIMILLION-GATE FPGAs
Authors: MA JING , ATHANAS PETER , HUANG XINMING
Published: December 2005

This paper presents an FPGA design methodology that can be used to shorten the FPGA design-and-debug cycle, especially as the gate counts increase to multimillions. Core-based incremental placement algorithms, in conjunction with fast interactive routing, are investigated to reduce the design processing time by distinguishing the changes between design iterations and reprocessing only the changed blocks without affecting the remaining part of the design. When combined with a background refinement thread, the incremental approach offers the instant gratification that designers expect, while preserving the fidelity attained through batch-oriented programs. An integrated FPGA design environment is then developed based on the incremental placer and its background refiner. The results show that the incremental design methodology is in orders of magnitude faster than the competing approaches such as the Xilinx M3 tools without sacrificing too much quality.
AN ULTRA LOW-POWER CURRENT-MODE SENSE AMPLIFIER FOR SRAM APPLICATIONS
Authors: KONG ZHI-HUI , YEO KIAT-SENG , CHANG CHIP-HONG
Published: December 2005

A novel micro-power current sense amplifier employing a cross-coupled current-mirror configuration is presented. The circuit is designed for low-voltage low-power SRAM applications. Its sensing speed is independent of the bit-line capacitances and is almost insensitive to the data-line capacitances. Extensive post-layout simulation results based on a 1.8 V/0.18 μm CMOS technology from Chartered Semiconductor Manufacturing Ltd. (CHRT) have verified that the new sense amplifier promises a much sought-after power-efficient advantage and a note-worthy power-delay product superiority over the conventional and recently reported sense amplifier circuits. These attributes of the proposed sense amplifier make it judiciously appropriate for use in the contemporary high-complexity regime, which incessantly craves for low-power characteristics.
Inhibition of thirst when dehydrated rats drink water or saline
Authors: Hoffmann Myriam L. , DenBleyker Megan , Smith James C. , Stricker Edward M.
Published: December 2005

The present experiments sought to identify the physiological signals that inhibit thirst when dehydrated rats drink water or NaCl solution. Rats were deprived of drinking fluid but not food overnight. When allowed to drink again, the dehydrated animals consumed water or saline (0.05 M, 0.10 M, 0.15 M, or 0.20 M NaCl solution) almost continuously for 5–8 min before stopping. The volumes consumed were similar regardless of which fluid they ingested, but blood analyses indicated that increased plasma osmolality and decreased plasma volume, or both, still remained when drinking terminated. These results suggest that the composition of the ingested fluid is less significant than its volume in providing an early signal that inhibits thirst and fluid consumption by dehydrated rats. Analyses of the gastrointestinal tracts revealed that the cumulative volume in the stomach and small intestine correlated highly with the amount consumed regardless of which fluid was ingested. These and other results suggest that the volume of fluid ingested by dehydrated rats is sensed by stretch receptors detecting distension of the stomach and small intestine, which provide an early inhibitory stimulus of thirst.
The Proatherogenic Role of T Cells Requires Cell Division and Is Dependent on the Stage of the Disease
Authors: Khallou-Laschet Jamila , Caligiuri Giuseppina , Groyer Emilie , Tupin Emanuel , Gaston Anh-Thu , Poirier Bruno , Kronenberg Mitchell , Cohen José L. , Klatzmann David , Kaveri Srini V. , Nicoletti Antonino
Published: December 2005

Objective—The mechanism by which T cells exert a proatherogenic potential is unclear. In order to determine whether this potential requires their replication, we crossed atherosclerosis-prone apolipoprotein E knockout mice (ApoE°) with transgenic mice in which exclusive and conditional ablation of dividing T cells relies on their specific expression of the herpes simplex type 1 thymidine kinase (TK) suicide gene.

Methods and Results—We first showed that conalbumin-immunized ApoE°TK mice mounted a significant immune response to the antigen that was fully and specifically blocked by an in vivo ganciclovir (GCV) treatment. Next, ApoE°TK mice and ApoE° mice were treated or not with GCV either during the first 4 weeks (GCV 1 to 4w), the last 4 weeks (GCV 5 to 8w), or during 8 weeks (GCV 1 to 8w). Strikingly, ApoE°TK mice displayed a dramatic decrease in lesion development in the GCV 1 to 8w and GCV 5 to 8w groups, whereas the GCV had no effect when administered during the first 4 weeks. In protected mice, the inflammatory parameters in lesions, the percentage of CD69+CD3+splenocytes, and the circulating natural killer T cells were reduced.

Conclusions—The present study, therefore, shows that the proatherogenic potential of T cells is crucial in the progression of fatty streaks to mature plaques and requires cell division.
Do Acute Diffusion- and Perfusion-Weighted MRI Lesions Identify Final Infarct Volume in Ischemic Stroke?
Authors: Rivers C.S. , Wardlaw J.M. , Armitage P.A. , Bastin M.E. , Carpenter T.K. , Cvoro V. , Hand P.J. , Dennis M.S.
Published: December 2005

Background and Purpose—

An acute mismatch on diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) may represent the “tissue-at-risk.” It is unclear which “semiquantitative” perfusion parameter most closely identifies final infarct volume.

Methods—

Acute stroke patients underwent DWI and PWI (dynamic-susceptibility contrast imaging) on admission (baseline), and T
2
-weighted imaging (T
2
WI) at 1 or 3 months after stroke. “Semiquantitative” mean transit time (MTT
sq
=first moment of concentration/time curve), cerebral blood volume (CBV
sq
=area under concentration/time curve), and cerebral blood flow (CBF
sq
=CBV
sq
/MTT
sq
) were calculated. DWI and PWI lesions were measured at baseline and final infarct volume on T
2
WI acquired ≥1 month after stroke. Baseline DWI, CBF
sq
, and MTT
sq
lesion volumes were compared with final T
2
WI lesion volume.

Results—

Among 46 patients, baseline DWI and CBF
sq
lesions were not significantly different from final T
2
WI lesion volume, but baseline MTT
sq
lesions were significantly larger. The correlation with final T
2
WI lesion volume was strongest for DWI (Spearman rank correlation coefficient ρ=0.68), intermediate for CBF
sq
(ρ=0.55), and weakest for MTT
sq
(ρ=0.49) baseline lesion volumes. Neither DWI/CBF
sq
nor DWI/MTT
sq
mismatch predicted lesion growth; lesion growth was equally common in those with and without mismatch.

Conclusions—

Of the 2 PWI parameters, CBF
sq
lesions most closely identifies, and MTT
sq
overestimates, final T
2
WI lesion volume. “DWI/PWI mismatch” does not identify lesion growth. Patients without “DWI/PWI mismatch” are equally likely to have lesion growth as those with mismatch and should not be excluded from acute stroke treatment.
Pushing around the Locus of Selection: Evidence for the Flexible-selection Hypothesis
Authors: Vogel Edward K. , Woodman Geoffrey F. , Luck Steven J.
Published: December 2005

Attention operates at an early stage in some experimental paradigms and at a late stage in others, which suggests that the locus of selection is flexible. The present study was designed to determine whether the locus of selection can vary flexibly within a single experimental paradigm as a function of relatively modest variations in stimulus and task parameters. In the first experiment, a new method for assessing the locus of selection was developed. Specifically, attention can influence perceptual encoding only if it is directed to the target before a perceptual representation of the target has been formed, whereas attention can influence postperceptual processes even if attention is cued after perception is complete. Event-related potentials were used to confirm the validity of this method. The subsequent experiments used cueing tasks in which subjects were required to perceive and remember a set of objects, and the difficulty of the perception and memory components of the task were varied. When the task overloaded perception but not working memory, attention influenced the formation of perceptual representations but not the storage of these representations in memory; when the task overloaded working memory but not perception, attention influenced the transfer of perceptual representations into memory but not the formation of the perceptual representations. Thus, attention operates to select relevant information at whatever stage or stages of processing are overloaded by a particular stimulus-task combination.
The Cerebral Response during Subjective Choice with and without Self-reference
Authors: Johnson Sterling C. , Schmitz Taylor W. , Kawahara-Baccus Tisha N. , Rowley Howard A. , Alexander Andrew L. , Lee Jonghoon , Davidson Richard J.
Published: December 2005

The anterior medial prefrontal (AMPFC) and retrosplenial (RSC) cortices are active during self-referential decision-making tasks such as when participants appraise traits and abilities, or current affect. Other appraisal tasks requiring an evaluative decision or mental representation, such as theory of mind and perspective-taking tasks, also involve these regions. In many instances, these types of decisions involve a subjective opinion or preference, but also a degree of ambiguity in the decision, rather than a strictly veridical response. However, this ambiguity is generally not controlled for in studies that examine self-referential decision-making. In this functional magnetic resonance imaging experiment with 17 healthy adults, we examined neural processes associated with subjective decision-making with and without an overt self-referential component. The task required subjective decisions about colors-regarding self-preference (internal subjective decision) or color similarity (external subjective decision) under conditions where there was no objectively correct response. Results indicated greater activation in the AMPFC, RSC, and caudate nucleus during internal subjective decision-making. The findings suggest that self-referential processing, rather than subjective judgments among ambiguous response alternatives, accounted for the AMPFC and RSC response.
Effects of Divided Attention on fMRI Correlates of Memory Encoding
Authors: Uncapher Melina R. , Rugg Michael D.
Published: December 2005

Performing a secondary task concurrently with a study task has a detrimental effect on later memory for studied items. To investigate the mechanisms underlying this effect, the processing resources available for an incidental encoding task were varied by manipulating secondary task difficulty. fMRI data were acquired as volunteers (n = 16) made animacy decisions to visually presented study words while concurrently performing either an easy or a hard auditory monitoring task. “Subsequent memory effects”-greater activity at study for words later remembered versus words later forgotten-were identified in the left ventral inferior frontal gyrus and the left anterior hippocampus. These effects did not vary according to whether the encoding task was performed concurrently with the easy or the hard secondary task. However, as secondary task difficulty increased, study-item activity declined and auditory-item activity increased in dorsolateral prefrontal and superior parietal regions that have been implicated in the support of executive and control functions. The findings suggest that dividing attention during encoding influences the probability of engaging the encoding operations that support later episodic memory, but does not alter the nature of the operations themselves. The findings further suggest that the probability of engaging these encoding operations depends on the level of general processing resources engaged in service of the study task.
Different Effects of Exogenous Cues in a Visual Detection and Discrimination Task: Delayed Attention Withdrawal and/or Speeded Motor Inhibition?
Authors: Lubbe Rob H. J. Van der , Vogel Rutger O. , Postma Albert
Published: December 2005

Several studies examining spatial attention have found a discrepancy regarding the effects of exogenous cues on reaction times in visual detection and discrimination tasks. Namely, across a wide range of cue-target intervals, responses are slower for targets at cued than at uncued locations (inhibition of return) in detection tasks, whereas responses are faster for targets at cued than at uncued locations (facilitation) in discrimination tasks. Two hypotheses were proposed to account for this discrepancy. First, attention may dwell much longer on the exogenously cued location in discrimination tasks because stimuli have to be identified (i.e., the delayed attention withdrawal hypothesis). Secondly, due to increased motor preparation in detection tasks, cue-induced motor inhibition may rise much faster in these tasks than in discrimination tasks (i.e., the speeded motor inhibition hypothesis). We examined to what extent these hypotheses can account for effects of exogenous cues in a detection and discrimination task on the extrastriate P1 component, and the onset of motor activation, as indexed by the lateralized readiness potential. Some support was found for the delayed attention withdrawal hypothesis, as task-dependent cueing effects were found on the P1 component. Other aspects of our data, however, indicate that motor inhibition is also involved. Based on these findings, we propose that effects of exogenous cues in detection and discrimination tasks are determined by the interplay between two mechanisms, of which the time courses of activation may be modulated by the specific setting.
Automatic Priming of Semantically Related Words Reduces Activity in the Fusiform Gyrus
Authors: Wheatley Thalia , Weisberg Jill , Beauchamp Michael S. , Martin Alex
Published: December 2005

We used rapid, event-related fMRI to identify the neural systems underlying object semantics. During scanning, subjects silently read rapidly presented word pairs (150 msec, SOA = 250 msec) that were either unrelated in meaning (ankle-carrot), semantically related (fork-cup), or identical (crow-crow). Activity in the left posterior region of the fusiform gyrus and left inferior frontal cortex was modulated by word-pair relationship. Semantically related pairs yielded less activity than unrelated pairs, but greater activity than identical pairs, mirroring the pattern of behavioral facilitation as measured by word reading times. These findings provide strong support for the involvement of these areas in the automatic processing of object meaning. In addition, words referring to animate objects produced greater activity in the lateral region of the fusiform gyri, right superior temporal sulcus, and medial region of the occipital lobe relative to manmade, manipulable objects, whereas words referring to manmade, manipulable objects produced greater activity in the left ventral premotor, left anterior cingulate, and bilateral parietal cortices relative to animate objects. These findings are consistent with the dissociation between these areas based on sensory-and motor-related object properties, providing further evidence that conceptual object knowledge is housed, in part, in the same neural systems that subserve perception and action.
Attention and Sensory Gain Control: A Peripheral Visual Process?
Authors: Handy Todd C. , Khoe Wayne
Published: December 2005

Attention-related sensory gain control in human extra-striate cortex is believed to improve the acuity of visual perception. Yet given wide variance in the spatial resolution of vision across the retina, it remains unclear whether sensory gain operates homogenously between foveal and nonfoveal retinotopic locations. To address this issue, we used event-related potentials (ERPs) in a variant of the canonical spatial attention task. Participants were cued to expect targets at either fixation (foveal targets) or at a location several degrees above fixation (parafoveal targets). At both target locations, manual reaction times were shorter for cued relative to uncued targets, indicating that attention was consistently oriented to the cued location. Nevertheless, attention-related increases in sensory-evoked cortical activity were only observed at the parafoveal target location, as measured by the amplitude of the lateral occipital P1 ERP component. A second experiment replicated this data pattern using targets with lower stimulus contrast, indicating that the absence of a P1 effect for foveal targets could not be attributed to a saturated P1 response under higher-contrast stimulus conditions. When considered in light of retinogeniculate projections to cortex showing systematic changes in their physiological organization beginning within a degree of visual angle of the fovea, our findings support the proposal that the strategic functions of visual attention may vary with the retinotopic location involved.
No "Sombre Satan": C. S. Lewis, Milton, and Re-presentations of the Diabolical
Authors: Stutz Chad
Published: December 2005

C.S. Lewis is most often read as a staunch "anti-Satanist" and critic of romanticized readings of Milton's Satan, a view derived largely from his Preface to Paradise Lost. Elsewhere, however, Lewis disagrees strongly with Milton's representations of Satan, Hell, and demons, most notably in his fictional works Perelandra, That Hideous Strength, and The Screwtape Letters. To rectify what he saw as the "harm" caused by Milton's humanized depiction of the diabolical, Lewis draws upon elements of a long medieval tradition which Milton had largely avoided—the tradition of "grotesque" representation. In appropriating this tradition, Lewis aims to re-introduce a sense of terror in connection with the diabolical, a move which both suggests the violence and brutality of certain forms of evil and disallows any sympathetic identification with the Devil on the part of the reader. In contrast to Milton, then, Lewis portrays a Devil that is aggressive and animalistic, and a Hell that is despotic and intrinsically unstable. At the same time, however, Lewis was keenly aware that especially in modern society the diabolical can often exist within the seemingly "normal," and his employment of the grotesque finally urges a chilling recognition of the terrible within each of us.
The Economy of Salvation: Narrative and Liminality in Rembrandt's Death of the Virgin
Authors: Bernier Ronald
Published: December 2005

This essay examines Rembrandt's 1639 etching, The Death of the Virgin, an image which, despite a comprehensive literature on the artist's graphic work, has received little critical attention beyond formal analyses of the print as evidence of the artist's stylistic transition from an elaborate Baroque sensibility, typical of the 1630s, to a more restrained vision of the 1640s. It considers the special nature of the depicted subject, the transitus of the Virgin from earthly to heavenly life and the promise that miracle holds for the eternal life of all believers. Taking into account official Protestant and Reformed iconoclast proscriptions of the cult of the Virgin, as well as the iconographic features of literary, visual and personal sources, the author re-interprets the subject of the spiritual mystery beyond a dominantly literal and narrative depiction of the moment of death, to an exegesis on the promise of and faith in salvation, specifically through the intercession of the Virgin, she who transcends finite mortality and who holds, according to the faithful, that special 'liminal' place between the divine and the earthly.
When He would Compose from Fragments a World Perfect at Last: Theology and Poetics in Czeslaw Milosz's "From the Rising of the Sun"
Authors: Stankiewicz David
Published: December 2005

This essay considers the place of religious and theological thought in the work of 20th century Nobel Laureate, Czeslaw Milosz (1911–2004). In a manner unique in contemporary world literature, Milosz approached and utilized these realms as a means to formulate and examine questions that are both timely and timeless. Focusing on sections I, II, and VII of the long poem-sequence, "From the Rising of the Sun," (along with discussions of other key poems and texts) the essay explores the dynamic interplay between theological thought and poetic craft in Milosz's work. Section I, "The Unveiling," introduces both the key themes the poem sequence explores (being and time, the meaning of history and individual lives, fall and redemption) as well as key poetic techniques (direct descriptive invocation and nuanced use of verb tense). Section II functions as a poetic embodiment of a particularly Miloszian, unorthodox "Manichaenism," an outlook that finds no basis for human values in the natural order of the world. Embedded in this section is a poetic gesture of hope that is more fully explored in Section VII. In this concluding section Milosz, using a full-range of poetic techniques ranging from the dramatic-narrative to the direct invocation of vanished reality, explores the heterodox theological concept of apokatastasis, or total restoration, as a gesture of profound hope that has theological, ethical, and aesthetic implications.
Netting the Butterfly Man: The Significance of Vladimir Nabokov in W. G. Sebald's The Emigrants
Authors: Shrayer Maxim , Curtin Adrian
Published: December 2005

In this essay, we examine the role of Vladimir Nabokov in W. G. Sebald's The Emigrants (1992; Eng. tr. 1996), both as a character in the novel (as the unannounced "butterfly man") and as an intertextual and metaphysical point of reference. It is our contention that this authorial intervention on Sebald's part may stem from the fact that both the German-born Sebald and the Russian-born Nabokov were spiritual witnesses to the Shoah, and though they were non-Jewish authors, they were committed to the artistic reckoning of this event through writing and memory. To this end, we offer a reading of The Emigrants that re-interprets the book in the light of Nabokov's continued presence, juxtaposing the artistic systems of these two authors and considering their respective approaches to catastrophe, as well as the shared possibility in their art that the human spirit may survive and endure.
By Popular Demand: The Effect of Public Opinion on Income Inequality
Authors: Andersen Robert , Heath Anthony , Weakliem David
Published: December 2005

This paper examines the relationship between public support for wage differentials and actual income inequality using data from the World Values Surveys. The distribution of income is more equal in nations where public opinion is more egalitarian. There is some evidence that the opinions of people with higher incomes are more influential than those of people with low incomes. Although the estimated relationship is stronger in democracies, it is present even under non-democratic governments, and the hypothesis that effects are equal cannot be rejected. We consider the possibility of reciprocal causation by means of an instrumental variables analysis, which yields no evidence that income distribution affects opinion.
Trust and National Character: Japanese Sense of Trust, Cross-National and Longitudinal Surveys
Authors: Yoshino Ryozo
Published: December 2005

This paper overviews people's sense of trust as it is reflected in the response data of questionnaire surveys. I will study the variability of people's trust systems in order to explore the stability over time and the change due to the short-term changes of economic and political conditions. To begin with, I will explain briefly the history of our longitudinal and cross-national survey on national character. Secondly, I will summarize some aspects of people's sense of trust in our longitudinal survey of Japanese national character. Thirdly, I will present cross-national comparative analysis of trust in our seven-country survey and our East Asia survey. Fourthly, I will consider the acculturation of the Japanese immigrants in Brazil, Hawaii, and the West Coast of USA. Finally, I will provide some comments on cross-national scaling of trust for our future research.
The Grand Strategy of Charles V (1500-1558): Castile, War, and Dynastic Priority in the Mediterranean
Authors: Espinosa Aurelio
Published: December 2005

This paper analyzes two imperial policies, the dynastic strategy of Charles V and the nationalist agenda of the Castilian clerical elite. The Protestant Reformation forced Charles to assess his priorities according to his conviction of religious unity and his dynastic claim of universal monarchy. Charles' ambitions compromised Spain's entrepreneurial agenda, which consisted of the defense of the Mediterranean against the Ottomans. Seeking to protect the coalescing transatlantic system and established commercial networks of Spanish businessmen, the Spanish administration under President Tavera (1524-1539) failed to convince Charles to focus on the Muslim enemy and to allow the German people to decide their own religious destinies. Instead, Charles sought to contain his universal monarchy in Europe, and his decision to restore religious unity in the empire resulted in the overextension of Spanish resources and the eventual decline of Spain.
Our Lady of the Rosary, African Slaves, and the Struggle Against Heretics in Brazil, 1550-1660
Authors: Meznar Joan
Published: December 2005

In the sixteenth and seventeenth centuries, as first French Huguenots and then Dutch Calvinists threatened Portuguese control of Brazil, Jesuit missionaries promoted devotion to Our Lady of the Rosary as a defense against both heresy and heretics. African slaves, as well as Indians and white settlers, were encouraged to join Confraternities of the Rosary in order to deepen their commitment to the Catholic faith and, by extension, to the Catholic political cause. Using sermons that the Jesuit father Antonio Vieira preached to black Confraternities of the Rosary, the article addresses the appeal these brotherhoods held for African slaves, and ways in which they became centers for the survival of African traditions in Catholic Brazil.
Measured Reciprocity: English Ambassadorial Gift Exchange in the 17th and 18th Centuries
Authors: Jansson Maija
Published: December 2005

This article examines the nature of ambassadorial gifting by placing the subject within the framework of the important works on gifts and giving. It explains the place of gifts within the ceremonials preceding negotiation, and the reason for that. Ultimately it shows how the value of ambassadorial gifts was calculated in order to create a certain reciprocity in giving.
Mineralogical controls on storage of As, Cu, Pb and Zn at the abandoned Mathiatis massive sulphide mine, Cyprus
Authors: Hudson-Edwards K. A. , Edwards S. J.
Published: December 2005

The Mathiatis massive sulphide deposit in Cyprus was a low-grade (0.3% Cu), three million ton ore body of pyrite and minor chalcopyrite occurring within basaltic lavas of the Troodos ophiolite. Cessation of mining in 1987 left a deep open pit surrounded by large heaps of spoil, which are undergoing oxidation and leaching. The aim of this study was to determine the mineralogical controls on the storage and potential remobilization of As, Cu, Pb and Zn within, and from, mine spoil heaps. Most of the spoil samples collected, and related materials (stream sediment, reaction zone between a boulder of massive pyrite and calcareous chert, salt crusts on stream beds), are enriched in As (27—220 ppm), Cu (110—400 ppm), Pb (10—140 ppm) and Zn (290—12,000 ppm) relative to both the basalt and calcareous chert (As 4—10 ppm, Cu 20—76 ppm, Pb 3—6 ppm, Zn 39—200 ppm).

Arsenic, Cu, Pb and Zn in the spoil and related materials are associated with Fe(-Al-S)-O, Fe(-Al-Mg)-S-O, Al(-Mg-Fe)-S-O and Mg(-Al-Fe)-S-O phases (the brackets represent minor components of less than 20 wt.% within the phases). Chemical extraction work using CaCl2 suggests that Cu, Zn and to some extent, As, are potentially more soluble than Pb. This is corroborated by the very high total concentrations of Cu and Zn in both the secondary salt crusts and the reaction zone material, high CaCl2-extractable As, Cu and Zn in the salt crusts, and aqueous data for the Mathiatis mine area collected for a European Union LIFE report. This may have implications for ecosystem health and water quality in the Mathiatis area and areas of similar mineralogy and climate world wide.
Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus
Authors: Beck Olaf , Topp Max S. , Koehl Ulrike , Roilides Emmanuel , Simitsopoulou Maria , Hanisch Mitra , Sarfati Jacqueline , Latgé Jean Paul , Klingebiel Thomas , Einsele Hermann , Lehrnbecher Thomas
Published: December 2005

Invasive aspergillosis remains a serious complication in patients undergoing allogeneic stem cell transplantation (SCT). Since it became clear that lymphocytes provide a critical secondary defense against fungi, adoptive transfer of functionally active anti-Aspergillus T cells might be an option to restore adaptive immune effector mechanisms. Using the interferon (IFN)-γ secretion assay, we isolated human activated T cells upon stimulation with a cellular extract of Aspergillus fumigatus. Culturing this cell population for 14 days, we obtained an average of 1.1 × 107 cells from a single 100-mL blood draw in 7 of 7 healthy individuals. Within another 14 days, these cells were expanded to an average number of 2.0 × 108 T-helper 1 (TH1) cells secreting IFN-γ on stimulation with Aspergillus antigens. Testing various fungal antigen extracts, similar proportions of IFN-γ-producing CD3+/CD4+ cells were obtained upon activation with antigen extracts of A fumigatus, A flavus, A niger, and Penicillium chrysogenum, whereas no significant IFN-γ production was observed upon activation with antigen extracts of Alternaria alternata and Candida albicans. In addition, generated T cells were able to induce damage to A fumigatus hyphae, and significantly increased hyphal damage induced by human neutrophils. CD4+ T-cell-mediated alloreactivity of generated anti-Aspergillus T cells was clearly reduced compared with that of the original cell population. In conclusion, we present a simple and feasible strategy for rapid generation of a high number of functional active T cells against Aspergillus from a single blood draw. Our data suggest that functionally active T cells against Aspergillus could be a promising treatment option for patients undergoing allogeneic SCT. (Blood. 2006;107: 2562-2569)
A new decoding algorithm for hidden Markov models improves the prediction of the topology of all-beta membrane proteins
Authors: Fariselli Piero , Martelli Pier Luigi , Casadio Rita
Published: December 2005

Background

Structure prediction of membrane proteins is still a challenging computational problem. Hidden Markov models (HMM) have been successfully applied to the problem of predicting membrane protein topology. In a predictive task, the HMM is endowed with a decoding algorithm in order to assign the most probable state path, and in turn the labels, to an unknown sequence. The Viterbi and the posterior decoding algorithms are the most common. The former is very efficient when one path dominates, while the latter, even though does not guarantee to preserve the HMM grammar, is more effective when several concurring paths have similar probabilities. A third good alternative is 1-best, which was shown to perform equal or better than Viterbi.

Results

In this paper we introduce the posterior-Viterbi (PV) a new decoding which combines the posterior and Viterbi algorithms. PV is a two step process: first the posterior probability of each state is computed and then the best posterior allowed path through the model is evaluated by a Viterbi algorithm.

Conclusion

We show that PV decoding performs better than other algorithms when tested on the problem of the prediction of the topology of beta-barrel membrane proteins.
Mining published lists of cancer related microarray experiments: Identification of a gene expression signature having a critical role in cell-cycle control
Authors: Finocchiaro Giacomo , Mancuso Francesco , Muller Heiko
Published: December 2005

Background

Routine application of gene expression microarray technology is rapidly producing large amounts of data that necessitate new approaches of analysis. The analysis of a specific microarray experiment profits enormously from cross-comparing to other experiments. This process is generally performed by numerical meta-analysis of published data where the researcher chooses the datasets to be analyzed based on assumptions about the biological relations of published datasets to his own data, thus severely limiting the possibility of finding surprising connections. Here we propose using a repository of published gene lists for the identification of interesting datasets to be subjected to more detailed numerical analysis.

Results

We have compiled lists of genes that have been reported as differentially regulated in cancer related microarray studies. We searched these gene lists for statistically significant overlaps with lists of genes regulated by the tumor suppressors p16 and pRB. We identified a highly significant overlap of p16 and pRB target genes with genes regulated by the EWS/FLI fusion protein. Detailed numerical analysis of these data identified two sets of genes with clearly distinct roles in the G1/S and the G2/M phases of the cell cycle, as measured by enrichment of Gene Ontology categories.

Conclusion

We show that mining of published gene lists in the absence of numerical detail about gene expression levels constitutes a fast, easy to perform, widely applicable, and unbiased route towards the identification of biologically related gene expression microarray datasets.
-In silico functional characterization of a double histone fold domain from the Heliothis zea virus 1
Authors: Greco Claudio , Fantucci Piercarlo , De Gioia Luca
Published: December 2005

Background

Histones are short proteins involved in chromatin packaging; in eukaryotes, two H2a-H2b and H3-H4 histone dimers form the nucleosomal core, which acts as the fundamental DNA-packaging element. The double histone fold is a rare globular protein fold in which two consecutive regions characterized by the typical structure of histones assemble together, thus originating a histone pseudodimer. This fold is included in a few prokaryotic histones and in the regulatory region of guanine nucleotide exchange factors of the Sos family. For the prokaryotic histones, there is no direct structural counterpart in the nucleosomal core particle, while the pseudodimer from Sos proteins is very similar to the dimer formed by histones H2a and H2b

Results

The absence of a H3-H4-like histone pseudodimer in the available structural databases prompted us to search for proteins that could assume such fold. The application of several secondary structure prediction and fold recognition methods allowed to show that the viral protein gi|22788712 is compatible with the structure of a H3-H4-like histone pseudodimer. Further in silico analyses revealed that this protein module could retain the ability of mediating protein-DNA interactions, and could consequently act as a DNA-binding domain.

Conclusion

Our results suggest a possible functional role in viral pathogenicity for this novel double histone fold domain; thus, the computational analyses here reported will be helpful in directing future biochemical studies on gi|22788712 protein.
High performance workflow implementation for protein surface characterization using grid technology
Authors: Merelli Ivan , Morra Giulia , D'Agostino Daniele , Clematis Andrea , Milanesi Luciano
Published: December 2005

Background

This study concerns the development of a high performance workflow that, using grid technology, correlates different kinds of Bioinformatics data, starting from the base pairs of the nucleotide sequence to the exposed residues of the protein surface. The implementation of this workflow is based on the Italian Grid.it project infrastructure, that is a network of several computational resources and storage facilities distributed at different grid sites.

Methods

Workflows are very common in Bioinformatics because they allow to process large quantities of data by delegating the management of resources to the information streaming. Grid technology optimizes the computational load during the different workflow steps, dividing the more expensive tasks into a set of small jobs.

Results

Grid technology allows efficient database management, a crucial problem for obtaining good results in Bioinformatics applications. The proposed workflow is implemented to integrate huge amounts of data and the results themselves must be stored into a relational database, which results as the added value to the global knowledge.

Conclusion

A web interface has been developed to make this technology accessible to grid users. Once the workflow has started, by means of the simplified interface, it is possible to follow all the different steps throughout the data processing. Eventually, when the workflow has been terminated, the different features of the protein, like the amino acids exposed on the protein surface, can be compared with the data present in the output database.
Systematic analysis of human kinase genes: a large number of genes and alternative splicing events result in functional and structural diversity
Authors: Milanesi Luciano , Petrillo Mauro , Sepe Leandra , Boccia Angelo , D'Agostino Nunzio , Passamano Myriam , Di Nardo Salvatore , Tasco Gianluca , Casadio Rita , Paolella Giovanni
Published: December 2005

Background

Protein kinases are a well defined family of proteins, characterized by the presence of a common kinase catalytic domain and playing a significant role in many important cellular processes, such as proliferation, maintenance of cell shape, apoptosys. In many members of the family, additional non-kinase domains contribute further specialization, resulting in subcellular localization, protein binding and regulation of activity, among others. About 500 genes encode members of the kinase family in the human genome, and although many of them represent well known genes, a larger number of genes code for proteins of more recent identification, or for unknown proteins identified as kinase only after computational studies.

Results

A systematic in silico study performed on the human genome, led to the identification of 5 genes, on chromosome 1, 11, 13, 15 and 16 respectively, and 1 pseudogene on chromosome X; some of these genes are reported as kinases from NCBI but are absent in other databases, such as KinBase. Comparative analysis of 483 gene regions and subsequent computational analysis, aimed at identifying unannotated exons, indicates that a large number of kinase may code for alternately spliced forms or be incorrectly annotated. An InterProScan automated analysis was perfomed to study domain distribution and combination in the various families. At the same time, other structural features were also added to the annotation process, including the putative presence of transmembrane alpha helices, and the cystein propensity to participate into a disulfide bridge.

Conclusion

The predicted human kinome was extended by identifiying both additional genes and potential splice variants, resulting in a varied panorama where functionality may be searched at the gene and protein level. Structural analysis of kinase proteins domains as defined in multiple sources together with transmembrane alpha helices and signal peptide prediction provides hints to function assignment. The results of the human kinome analysis are collected in the KinWeb database, available for browsing and searching over the internet, where all results from the comparative analysis and the gene structure annotation are made available, alongside the domain information. Kinases may be searched by domain combinations and the relative genes may be viewed in a graphic browser at various level of magnification up to gene organization on the full chromosome set.
HomoMINT: an inferred human network based on orthology mapping of protein interactions discovered in model organisms
Authors: Persico Maria , Ceol Arnaud , Gavrila Caius , Hoffmann Robert , Florio Arnaldo , Cesareni Gianni
Published: December 2005

Background

The application of high throughput approaches to the identification of protein interactions has offered for the first time a glimpse of the global interactome of some model organisms. Until now, however, such genome-wide approaches have not been applied to the human proteome.

Results

In order to fill this gap we have assembled an inferred human protein interaction network where interactions discovered in model organisms are mapped onto the corresponding human orthologs. In addition to a stringent assignment to orthology classes based on the InParanoid algorithm, we have implemented a string matching algorithm to filter out orthology assignments of proteins whose global domain organization is not conserved. Finally, we have assessed the accuracy of our own, and related, inferred networks by benchmarking them against i) an assembled experimental interactome, ii) a network derived by mining of the scientific literature and iii) by measuring the enrichment of interacting protein pairs sharing common Gene Ontology annotation.

Conclusion

The resulting networks are named HomoMINT and HomoMINT_filtered, the latter being based on the orthology table filtered by the domain architecture matching algorithm. They contains 9749 and 5203 interactions respectively and can be analyzed and viewed in the context of the experimentally verified interactions between human proteins stored in the MINT database. HomoMINT is constantly updated to take into account the growing information in the MINT database.
A Hybrid Genetic-Neural System for Predicting Protein Secondary Structure
Authors: Armano Giuliano , Mancosu Gianmaria , Milanesi Luciano , Orro Alessandro , Saba Massimiliano , Vargiu Eloisa
Published: December 2005

Background

Due to the strict relation between protein function and structure, the prediction of protein 3D-structure has become one of the most important tasks in bioinformatics and proteomics. In fact, notwithstanding the increase of experimental data on protein structures available in public databases, the gap between known sequences and known tertiary structures is constantly increasing. The need for automatic methods has brought the development of several prediction and modelling tools, but a general methodology able to solve the problem has not yet been devised, and most methodologies concentrate on the simplified task of predicting secondary structure.

Results

In this paper we concentrate on the problem of predicting secondary structures by adopting a technology based on multiple experts. The system performs an overall processing based on two main steps: first, a "sequence-to-structure" prediction is enforced by resorting to a population of hybrid (genetic-neural) experts, and then a "structure-to-structure" prediction is performed by resorting to an artificial neural network. Experiments, performed on sequences taken from well-known protein databases, allowed to reach an accuracy of about 76%, which is comparable to those obtained by state-of-the-art predictors.

Conclusion

The adoption of a hybrid technique, which encompasses genetic and neural technologies, has demonstrated to be a promising approach in the task of protein secondary structure prediction.