bluuebunny/crossref_metadata_2025 huggingface dataset:
A new instrument to expose the human larynx
Authors: Morgado Plínio Ferreira
Published: February 2005

OBJECTIVE

To present a nonwalled all‐detachable retractor that simultaneously exposes the mouth, pharynx, and larynx.

STUDY DESIGN AND SETTING

The proposed instrument is composed of a mouth‐gag with a set of 5 interchangeable angled tongue blades, and a pharyngeal lever that provides internal laryngo‐pharyngeal distension. Sixty‐five patients were submitted to tonsillectomy, adenoidectomy, and endolaryngeal surgery with the workspace provided by the manufactured scope.

RESULTS

Proper exposure of the upper aerodigestive tract was achieved in all patients. Naked eye, varied endoscopes, and special curved instruments were used to examine, lase, and manipulate tissues. Bimanual surgery was possible due to self‐retaining adjustment and a clamp for endoscopes.

CONCLUSION AND SIGNIFICANCE

This instrument allowed for an ample exposure from mouth to glottis in adults and children. Opposed to linear laryngoscopes in which the patient adapts to the instrument, its unique design adjusts to patients’ anatomy and to many clinical situations.
Management of congenital subglottic hemangioma: Trends and success over the past 17 years
Authors: Bitar Mohamed A. , Moukarbel Roger V. , Zalzal George H.
Published: February 2005

OBJECTIVE

To evaluate the success and complications of various treatment options of congenital subglottic hemangioma.

STUDY DESIGN AND SETTINGS

Reported cases were grouped by treatment modalities and corresponding outcome evaluated.

RESULTS

From 1986 through 2002, 372 patients were reported in 28 series. Carbon dioxide laser had 88.9% success rate yet 5.5 % significant subglottic stenosis. It shortened the tracheotomy duration by 13.7 months. Corticosteroids were not that beneficial (useful in only 24.5%) with 12.9% side effects. Intralesional corticosteroids were successful in 86.4% with 5.6% complication rate. Surgical excision (as young as 2.5 months), was useful in 98% with 10% complication rate, using cartilage grafts in 34%. Other modalities were less popular.

CONCLUSION

Treatment should be individualized. Guidelines are suggested. Priority is given to secure the airways. The CO2 laser is useful when used cautiously. Steroids may be beneficial. Excision is for stubborn cases.
The effect of polysomnography on pediatric adenotonsillectomy postoperative management
Authors: Rieder Anthony A. , Flanary Valerie
Published: February 2005

OBJECTIVE

We retrospectively investigated the effect and predictability of preoperative polysomnography (PSG) on the postoperative course of younger pediatric patients undergoing adenotonsillectomy.

STUDY DESIGN AND SETTING

A retrospective chart review was performed for patients 3 years of age and younger who had undergone adenotonsillectomy between July 1997 and July 2002 at the Children's Hospital of Wisconsin.

RESULTS

Two hundred eighty‐two patients were identified. Forty‐three patients had preoperative PSG. No correlation between the severity of PSG results and postoperative course was identified.

CONCLUSIONS

The role of PSG in upper airway obstruction and OSA remains controversial. This study suggests that although the complication rate may be higher in this younger population, these complications do not appear to have a large impact on their length of stay.

SIGNIFICANCE

This study suggests that the 3‐years‐and‐younger group, in the absence of other comorbidities, can safely undergo adenotonsillectomy without undergoing preoperative PSG. EBM raing: C.
Seasonal variation in Sarcocystis species infections in goats in northern Iraq
Authors: BARHAM M. , STÜTZER H. , KARANIS P. , LATIF B. M. , NEISS W. F.
Published: January 2005

We investigated the prevalence of sarcocystosis in 826 goats slaughtered in the winter season from November to April in northern Iraq. The prevalence of macrocysts was on average 34%, with only 20% infected animals in November, but 46% in February. The infection rate in 1-, 3- and 6-year-old goats was 4%, 48%, and 83%, respectively. The highest specificity of infection was in the oesophagus (99%) and the lowest in the diaphragm (3%). Grossly, we identified 2 forms of macroscopic sarcocysts, fat and thin, with different morphological characteristics. The prevalence of microcysts was 97% and no effects of age, sex and seasonal variations were observed. Development of microcysts in the small intestine of dogs and cats has also been investigated. The pre-patent period in experimentally infected dogs was 12–14 days and the patent period lasted 64–66 days. A dog shed about 155 million sporocysts, but no sporocysts were shed by cats that had been fed the same infected tissues, thus identifying the microcysts as Sarcocystis capracanis.
LIBERTARIANISM AT TWIN HARVARD
Authors: Lomasky Loren E.
Published: February 2005

In this essay Loren Lomasky wryly proposes that the views of Rawls and
Nozick might not be as radically divergent as is conventionally supposed.
To demonstrate this proposition, Lomasky invents “Twin Harvard”
counterparts of Rawls and Nozick. The twist is that Twin Rawls turns out to
be a leading libertarian theorist while Twin Nozick endorses a regime of
sweeping redistribution. In each case the position follows from familiar
elements in the theories of their respective, real-world counterparts.
Lomasky concludes that Twin Rawls actually makes better use of familiar
Rawlsian themes-such as the veil of ignorance, strains of commitment, and
the priority of liberty-than does Rawls himself. Moreover, Rawls's own
attempts at combating libertarianism are seen to be weak, sometimes
embarrassingly so. Libertarianism is a specter that he devoutly wishes to
exorcize, but cannot. Conversely, the rejection of libertarianism by Twin
Nozick (and Nozick?) is striking but shallow.
BEGGING THE QUESTION WITH STYLE: ANARCHY, STATE, AND UTOPIA
AT THIRTY YEARS
Authors: Fried Barbara H.
Published: February 2005

At 30 years' distance, it is safe to say that Nozick's Anarchy,
State and Utopia has achieved the status of a classic. It is not only the
central text for all contemporary academic discussions of libertarianism;
with Rawls's A Theory of Justice, it arguably frames the landscape of
academic political philosophy in second half of 20th century. Many factors,
obviously account for the prominence of the book. This paper considers one:
the book's use of rhetoric to charm and disarm its readers,
simultaneously establishing Nozick's credibility with readers, turning
them on his ideological opponents, and helping his argument over some of its
more serious substantive difficulties.
Further exploration of the effect of “diagnosis threat” on cognitive performance in individuals with mild head injury
Authors: SUHR JULIE A. , GUNSTAD JOHN
Published: February 2005

The present study further explored the phenomenon of “diagnosis threat” (Suhr & Gunstad, 2002), by examining the potential explanatory roles of anxiety, effort, and depression. Individuals with mild head injury history were randomly assigned to receive either neutral instructions (controls,N= 25) or to have attention called to their head injury history as a reason for invitation into the study (diagnosis threat,N= 28). Depression was measured at baseline. Following the neuropsychological battery, ratings of effort, test pressure, and state anxiety were completed. The diagnosis threat group performed worse than controls on attention/working memory, psychomotor speed, and memory tasks, but not on measures of executive functioning, post-test anxiety, or effort. Effort, anxiety and depression were not related to cognitive performance, nor did depression interact with expectations in explaining group differences in performance. Results provide further support for the “diagnosis threat” effect, but offer no support for effort, anxiety, or depression explanations for diminished performance. (JINS, 2005,11, 23–29.)
Retrograde amnesia for semantic information in Alzheimer's disease
Authors: MEETER MARTIJN , KOLLEN ARIANE , SCHELTENS PHILIP
Published: February 2005

Patients with mild to moderate Alzheimer's disease and normal controls were tested on a retrograde amnesia test with semantic content (Neologism and Vocabulary Test, or NVT), consisting of neologisms to be defined. Patients showed a decrement as compared to normal controls, pointing to retrograde amnesia within semantic memory. No evidence for a gradient within this amnesia was found, although one was present on an autobiographic test of retrograde amnesia that had a wider time scale. Several explanations for these results are presented, including one that suggests that extended retrograde amnesia and semantic memory deficits are in fact one and the same deficit. (JINS, 2005,11, 40–48.)
Standard regression-based methods for measuring recovery after
sport-related concussion
Authors: McCREA MICHAEL , BARR WILLIAM B. , GUSKIEWICZ KEVIN , RANDOLPH CHRISTOPHER , MARSHALL STEPHEN W. , CANTU ROBERT , ONATE JAMES A. , KELLY JAMES P.
Published: February 2005

Clinical decision making about an athlete's return to
competition after concussion is hampered by a lack of systematic
methods to measure recovery. We applied standard regression-based
methods to statistically measure individual rates of impairment at
several time points after concussion in college football players.
Postconcussive symptoms, cognitive functioning, and balance were
assessed in 94 players with concussion (based on American Academy of
Neurology Criteria) and 56 noninjured controls during preseason
baseline testing, and immediately, 3 hr, and 1, 2, 3, 5, and 7 days
postinjury. Ninety-five percent of injured players exhibited acute
concussion symptoms and impairment on cognitive or balance testing
immediately after injury, which diminished to 4% who reported elevated
symptoms on postinjury day 7. In addition, a small but clinically
significant percentage of players who reported being symptom free by
day 2 continued to be classified as impaired on the basis of objective
balance and cognitive testing. These data suggest that
neuropsychological testing may be of incremental utility to subjective
symptom checklists in identifying the residual effects of sport-related
concussion. The implementation of neuropsychological testing to detect
subtle cognitive impairment is most useful once postconcussive symptoms
have resolved. This management model is also supported by practical and
other methodological considerations. (JINS, 2005, 11,
58–69.)
Atmospheric CO2 uptake by a coastal upwelling system
Authors: Hales Burke , Takahashi Taro , Bandstra Leah
Published: February 2005

A biological pump for transferring atmospheric CO2 to deep ocean regimes has been identified in the upwelling zone of the U.S. Pacific coast off Oregon using high‐resolution measurements of PCO2 and nutrient concentrations that were made in May through August 2001. Surface water over most of the shelf was a strong sink for atmospheric CO2, while a narrow nearshore strip was an intense source. The dominance of the low‐CO2 waters over the shelf area makes the region a net sink during upwelling season. This is due to (1) upwelled water that carries abundant preformed nutrients, (2) complete photosynthetic uptake of these excess nutrients and a stoichiometric proportion of CO2, and (3) moderate warming of upwelled waters. If the remaining North Pacific's eastern boundary area is assumed to have similar conditions, this area should represent a sink of atmospheric CO2 that is 5% of the annual North Pacific CO2 uptake, and roughly equivalent to the North Pacific's uptake in the summer season. By mid‐August, PCO2 in subsurface waters increased 20–60%, corresponding to a 1.0–2.3% TCO2 increase, due to respiration of settling biogenic debris. This water would be transported off the shelf to depth by winter downwelling flow, providing an important mechanism for sequestering atmospheric CO2 into the oceans' interior.
The origin of the Tsushima Current based on oxygen isotope measurement
Authors: Kim Kyung‐Ryul , Cho Yang‐Ki , Kang Dong‐Jin , Ki Jun‐Hak
Published: February 2005

The origin of the Tsushima Current (TC) is still under debate since direct current observation data are rare and spatial differences in temperature and salinity are too minor to determine the path of the TC. Oxygen isotope is proved to be powerful for tracing the origin of the TC. Oxygen isotope data suggest that there are two water sources of the TC. The TC water could be classified into two water masses with different paths. The depleted oxygen isotope water originates from the Taiwan Strait (T‐TC), whereas the enriched oxygen isotope water originates directly from the Kuroshio (K‐TC).
Chronology and complex volcanic processes during the 2002–2003 flank eruption at Stromboli volcano (Italy) reconstructed from direct observations and surveys with a handheld thermal camera
Authors: Calvari Sonia , Spampinato Letizia , Lodato Luigi , Harris Andrew J. L. , Patrick Matthew R. , Dehn Jonathan , Burton Michael R. , Andronico Daniele
Published: February 2005

Effusive activity at Stromboli is uncommon, and the 2002–2003 flank eruption gave us the opportunity to observe and analyze a number of complex volcanic processes. In particular, the use of a handheld thermal camera during the eruption allowed us to monitor the volcano even in difficult weather and operating conditions. Regular helicopter‐borne surveys with the thermal camera throughout the eruption have significantly improved (1) mapping of active lava flows; (2) detection of new cracks, landslide scars, and obstructions forming within and on the flanks of active craters; (3) observation of active lava flow field features, such as location of new vents, tube systems, tumuli, and hornitos; (4) identification of active vent migration along the Sciara del Fuoco; (5) monitoring of crater's inner morphology and maximum temperature, revealing magma level changes within the feeding conduit; and (6) detection of lava flow field endogenous growth. Additionally, a new system developed by A. J. L. Harris and others has been applied to our thermal data, allowing daily calculation of effusion rate. These observations give us new insights on the mechanisms controlling the volcanic system.
Fuzzy exemplar‐based inference system for flood forecasting
Authors: Chang Li‐Chiu , Chang Fi‐John , Tsai Ya‐Hsin
Published: February 2005

Fuzzy inference systems have been successfully applied in numerous fields since they can effectively model human knowledge and adaptively make decision processes. In this paper we present an innovative fuzzy exemplar‐based inference system (FEIS) for flood forecasting. The FEIS is based on a fuzzy inference system, with its clustering ability enhanced through the Exemplar‐Aided Constructor of Hyper‐rectangles algorithm, which can effectively simulate human intelligence by learning from experience. The FEIS exhibits three important properties: knowledge extraction from numerical data, knowledge (rule) modeling, and fuzzy reasoning processes. The proposed model is employed to predict streamflow 1 hour ahead during flood events in the Lan‐Yang River, Taiwan. For the purpose of comparison the back propagation neural network (BPNN) is also performed. The results show that the FEIS model performs better than the BPNN. The FEIS provides a great learning ability, robustness, and high predictive accuracy for flood forecasting.
Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1)
Authors: McNamara Fergal N , Randall Andrew , Gunthorpe Martin J
Published: February 2005

We have characterised the effects of piperine, a pungent alkaloid found in black pepper, on the human vanilloid receptor TRPV1 using whole‐cell patch‐clamp electrophysiology.

Piperine produced a clear agonist activity at the human TRPV1 receptor yielding rapidly activating whole‐cell currents that were antagonised by the competitive TRPV1 antagonist capsazepine and the non‐competitive TRPV1 blocker ruthenium red.

The current–voltage relationship of piperine‐activated currents showed pronounced outward rectification (25±4‐fold between −70 and +70 mV) and a reversal potential of 0.0±0.4 mV, which was indistinguishable from that of the prototypical TRPV1 agonist capsaicin.

Although piperine was a less potent agonist (EC50=37.9±1.9 μM) than capsaicin (EC50=0.29±0.05 μM), it demonstrated a much greater efficacy (approximately two‐fold) at TRPV1.

This difference in efficacy did not appear to be related to the proton‐mediated regulation of the receptor since a similar degree of potentiation was observed for responses evoked by piperine (230±20%, n=11) or capsaicin (284±32%, n=8) upon acidification to pH 6.5.

The effects of piperine upon receptor desensitisation were also unable to explain this effect since piperine resulted in more pronounced macroscopic desensitisation (t1/2=9.9±0.7 s) than capsaicin (t1/2>20 s) and also caused greater tachyphylaxis in response to repetitive agonist applications.

Overall, our data suggest that the effects of piperine at human TRPV1 are similar to those of capsaicin except for its propensity to induce greater receptor desensitisation and, rather remarkably, exhibit a greater efficacy than capsaicin itself. These results may provide insight into the TRPV1‐mediated effects of piperine on gastrointestinal function.

British Journal of Pharmacology (2005) 144, 781–790. doi:10.1038/sj.bjp.0706040
Inhibition of the human two‐pore domain potassium channel, TREK‐1, by fluoxetine and its metabolite norfluoxetine
Authors: Kennard Louise E , Chumbley Justin R , Ranatunga Kishani M , Armstrong Stephanie J , Veale Emma L , Mathie Alistair
Published: February 2005

Block of the human two‐pore domain potassium (2‐PK) channel TREK‐1 by fluoxetine (ProzacR) and its active metabolite, norfluoxetine, was investigated using whole‐cell patch‐clamp recording of currents through recombinant channels in tsA 201 cells.

Fluoxetine produced a concentration‐dependent inhibition of TREK‐1 current that was reversible on wash. The IC50 for block was 19 μM. Block by fluoxetine was voltage‐independent. Fluoxetine (100 μM) produced an 84% inhibition of TREK‐1 currents, but only a 31% block of currents through a related 2‐PK channel, TASK‐3.

Norfluoxetine was a more potent inhibitor of TREK‐1 currents with an IC50 of 9 μM. Block by norfluoxetine was also voltage‐independent.

Truncation of the C‐terminus of TREK‐1 (Δ89) resulted in a loss of channel function, which could be restored by intracellular acidification or the mutation E306A. The mutation E306A alone increased basal TREK‐1 current and resulted in a loss of the slow phase of TREK‐1 activation.

Progressive deletion of the C‐terminus of TREK‐1 had no effect on the inhibition of the channel by fluoxetine. The E306A mutation, on the other hand, reduced the magnitude of fluoxetine inhibition, with 100 μM producing only a 40% inhibition.

It is concluded that fluoxetine and norfluoxetine are potent inhibitors of TREK‐1. Block of TREK‐1 by fluoxetine may have important consequences when the drug is used clinically in the treatment of depression.

British Journal of Pharmacology (2005) 144, 821–829. doi:10.1038/sj.bjp.0706068
Giant asymmetry of the processes of separation and homogenization of 3He–4He solid mixtures
Authors: Grigor’ev V. N. , Maidanov V. A. , Penzev A. A. , Polev A. V. , Rubets S. P. , Rudavskii E. Ya. , Rybalko A. S. , Syrnikov Ye. V.
Published: February 2005

A comparison of the kinetics of the separation processes and homogenization of 3He–4He solid mixtures is made with the use of precision barometry for samples of three types—dilute mixtures of 3He in 4He and of 4He in 3He and concentrated 3He–4He mixtures. It is found that in all types of mixtures studied the rate of the initial stage of homogenization can exceed the rate of separation by more than 500 times. An appreciable rate of phase separation in the concentrated mixtures, where, according to existing ideas, the impurity atoms in quantum crystals should be localized, attests to a new, unknown mechanism of mass transfer under those conditions, while the fast homogenization indicates that this process is nondiffusional in nature.
Spin-polarized electron tunneling between charge-density-wave metals
Authors: Ekino T. , Gabovich A. M. , Voitenko A. I.
Published: February 2005

For junctions between metals partially gapped by charge density waves (CDWs), the quasiparticle tunnel currents J(V) and conductances G(V) in external magnetic fields H are calculated as functions of H, the bias voltage V, temperature T, the dielectric gaps Σ, and the gapped portions μ of the Fermi surface (FS). The paramagnetic effect of H is taken into account, whereas orbital effects are neglected. General expressions are obtained for different CDW metal electrodes. Analytical formulas are obtained for T=0. Explicit numerical calculations are carried out for symmetrical junctions. The results are substantially unlike those for junctions between superconductors. It is shown that due to the interplay between quasiparticles from nested and non-nested FS sections the junction properties involve features appropriate to both symmetrical and asymmetrical setups. In particular, for H=0 discontinuities at eV=±2Σ and square-root singularities at eV=±Σ should coexist. Here e is the elementary charge. For H≠0 the former remain intact, while the latter split. It is suggested to use the splitting as a verification of the CDW nature of the pseudogap in high-Tc superconducting oxides.
Degradation and recovery of polarization under synchrotron x rays in SrBi2Ta2O9 ferroelectric capacitors
Authors: Menou N. , Castagnos A.-M. , Muller Ch. , Goguenheim D. , Goux L. , Wouters D. J. , Hodeau J.-L. , Dooryhee E. , Barrett R.
Published: January 2005

Elementary Pt∕SrBi2Ta2O9∕Pt ferroelectric capacitors have been structurally characterized by x-ray diffraction using highly brilliant synchrotron radiation. A microstructural analysis of the stacked layers was performed from the collection of high-quality one-dimensional and two-dimensional diffraction patterns. During x-ray diffraction experiments, peculiar electrical behaviors under irradiation were evidenced. Indeed, depending upon their initial state (poled or nonpoled), the capacitors have exhibited drastic changes in their electrical characteristics after or under irradiation, both “fatiguelike” (polarization reduction) and∕or “imprintlike” (voltage shift) phenomena being observed. Using a sample environment specially designed to measure in situ the evolutions of ferroelectric characteristics, the kinetics of both degradation and restoration of ferroelectric properties of the SrBi2Ta2O9-based capacitors under x-ray radiation have been analyzed. Reduction and recovery of switchable polarization have been explained in terms of interaction between ferroelectric domain configuration and photoinduced charge carriers. Mechanisms of charge trapping proposed in the literature are discussed to explain aging and rejuvenation.
The effect of water quality on cattle performance on pasture
Authors: Lardner H. A. , Kirychuk B. D. , Braul L. , Willms W. D. , Yarotski J.
Published: February 2005

In western Canada, dugouts are the primary source of water for beef cattle during the summer months. Over time, drought conditions and/or direct access by grazing animals have a negative effect on water constituents and overall water quality. A study was conducted to determine the effects of improvements in water quality on cattle performance. The effect of pasture water quality on weight gain of beef cattle was assessed with 44 Hereford yearling steers over 5 years and 40 Angus cow–calf pairs over 3 years. From 1999 to 2003, cattle were allocated to 1 of 4 treatments, which comprised untreated dugout water pumped to a trough, aerated water pumped to a trough, and coagulated and chlorinated water pumped to a trough, all compared with direct access by livestock to the water source. Data were collected on livestock weight gains, water consumption, fecal parasites, environmental conditions, water chemistry, biological constituents, and forage production and quality. Water treatment by aeration or coagulation tended to improve steer weight gains (P < 0.05) over untreated water from a dugout in 3 of 5 years. Daily weight gains tended to be improved slightly by simply pumping water to a trough without treatment. Water aerated and pumped to a trough in early summer tended to produce greater (P < 0.05) weight gains in calves than those drinking directly from the dugout. The effect of treatment on improving cattle weight gains appeared to be related to improved water palatability, which increased water and feed consumption. Water chemistry and biological constituents analysed did not identify significant differences among treatments. These results suggest that improving water quality with aeration and pumping to a trough will improve weight gain 9–10% over a 90-day grazing period in most years.
Effects of tissue culture, biolistic transformation, and introduction of PPO and SPS gene constructs on performance of sugarcane clones in the field
Authors: Vickers J. E. , Grof C. P. L. , Bonnett G. D. , Jackson P. A. , Morgan T. E.
Published: February 2005

Stably transformed sugarcane plants were produced by the biolistic introduction of DNA into tissue-cultured cells. Constructs containing genes in sense and antisense orientation of polyphenol oxidase and sense orientation of sucrose phosphate synthase were used in the transformations. Regenerated plants were grown in a series of field experiments that incorporated commercial varieties, including Q117, from which the transgenic clones were derived and plants regenerated from tissue culture but not subjected to biolistic bombardment. In all experiments, the mean yield of transgenic sugarcane was lower than commercial varieties and the transgenic clones often exhibited lower sugar content, although individual transgenic clones in some experiments were not significantly different from Q117. Those plants regenerated from tissue culture but not bombarded were intermediate in their yield, and more clones were equivalent to Q117 in agronomic performance. Transformed plants produced by the bombardment of callus performed poorly but the results from the tissue-cultured controls indicated that not all of this could be due to somaclonal variation. Some aspect(s) of the process of transformation itself was deleterious and in most cases more significant than the effects due to tissue culture. Of the transgenic clones grown at Ayr, Queensland, 1.6% were equivalent to Q117 in sugar content and yield, suggesting that large numbers of transgenic clones would have to be generated using the current method in order to allow for selection of clones with acceptable agronomic performance.
Inference of combinatorial regulation in yeast transcriptional networks: A case study of sporulation
Authors: Wang Wei , Cherry J. Michael , Nochomovitz Yigal , Jolly Emmitt , Botstein David , Li Hao
Published: February 2005

Decomposing transcriptional regulatory networks into functional modules and determining logical relations between them is the first step toward understanding transcriptional regulation at the system level. Modules based on analysis of genome-scale data can serve as the basis for inferring combinatorial regulation and for building mathematical models to quantitatively describe the behavior of the networks. We present here an algorithm called
modem
to identify target genes of a transcription factor (TF) from a single expression experiment, based on a joint probabilistic model for promoter sequence and gene expression data. We show how this method can facilitate the discovery of specific instances of combinatorial regulation and illustrate this for a specific case of transcriptional networks that regulate sporulation in the yeast
Saccharomyces cerevisiae
. Applying this method to analyze two crucial TFs in sporulation, Ndt80p and Sum1p, we were able to delineate their overlapping binding sites. We proposed a mechanistic model for the competitive regulation by the two TFs on a defined subset of sporulation genes. We show that this model accounts for the temporal control of the “middle” sporulation genes and suggest a similar regulatory arrangement can be found in developmental programs in higher organisms.
Molecular characterization of proteolytic cleavage sites of the
Pseudomonas syringae
effector AvrRpt2
Authors: Chisholm Stephen T. , Dahlbeck Douglas , Krishnamurthy Nandini , Day Brad , Sjolander Kimmen , Staskawicz Brian J.
Published: February 2005

During infection of
Arabidopsis thaliana
, the bacterium
Pseudomonas syringae
pv
tomato
delivers the effector protein AvrRpt2 into the plant cell cytosol. Within the plant cell, AvrRpt2 undergoes N-terminal processing and causes elimination of
Arabidopsis
RIN4. Previous work established that AvrRpt2 is a putative cysteine protease, and AvrRpt2 processing and RIN4 elimination require an intact predicted catalytic triad in that AvrRpt2. In this work, proteolytic events that depend on AvrRpt2 activity were characterized. The amino acid sequence surrounding the processing site of AvrRpt2 and two related sequences from RIN4 triggered Avr-Rpt2-dependent proteolytic cleavage of a synthetic substrate, demonstrating that these sequences are cleavage recognition sites for AvrRpt2 activity. Processing-deficient AvrRpt2 mutants were identified and shown to retain their ability to eliminate wild-type RIN4. Single amino acid substitutions were made in each of the two RIN4 cleavage sites, and mutation of both sites resulted in cleavage-resistant RIN4. Growth of
Pseudomonas
expressing AvrRpt2 was significantly higher than catalytically inactive mutants on
Arabidopsis rin4
/
rps2
mutant plants, suggesting there are additional protein targets of AvrRpt2 that account for the virulence activity of this effector. Bioinformatics analysis identified putative
Arabidopsis
proteins containing sequences similar to the proteolytic cleavage sites conserved in AvrRpt2 and RIN4. Several of these proteins were eliminated in an AvrRpt2-dependent manner in a transient
in planta
expression system. These results identify amino acids important for AvrRpt2 substrate recognition and cleavage as well as demonstrate AvrRpt2 protease activity eliminates multiple
Arabidopsis
proteins in a transient expression system.
T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-γ promoter via a conserved T-box half-site
Authors: Tong Yingkai , Aune Thomas , Boothby Mark
Published: February 2005

Promoter DNA methylation is a major epigenetic mechanism for silencing genes and establishing commitment in cells differentiating from their precursors. The transcription factor T-bet is a key determinant of IFN-γ gene expression in helper T cells, but the mechanisms by which it achieves this effect are not clear. It is shown here that T-bet binds to a highly conserved T-box half-site in the IFN-γ promoter, is recruited to the endogenous IFN-γ promoter in T lymphoid cells, and transactivates gene expression through this sequence in a manner dependent on consensus T-box residues. This conserved promoter site is methylated in a model T cell line, and enforced T-bet expression did not alter its complete methylation. T-bet transactivated the conserved core promoter in transfection assays and collaborated functionally with C/EBPβ despite methylation of the conserved element. Importantly, enforced T-bet expression led to dissociation of the mSin3a corepressor from the endogenous, chromatinized IFN-γ promoter without decreasing loading of the methyl-CpG binding protein MeCP2. These data indicate that T-bet can override repressive epigenetic modification by a mechanism in which this master regulator acts through a T-box half-site to enforce the activation of IFN-γ gene expression in part by decreased loading of a corepressor on methylated DNA.
Brain correlates of subjective reality of physically and psychologically induced pain
Authors: Raij Tuukka T. , Numminen Jussi , Närvänen Sakari , Hiltunen Jaana , Hari Riitta
Published: February 2005

Meaningful behavior requires successful differentiation of events surfacing from one's mind from those arising from the external world. Such judgements may be especially demanding during pain because of the strong contribution from psychological factors to this experience. It is unknown how the subjective reality of pain (SRP) is constructed in the human brain, and neuronal mechanisms of the subjective reality are poorly understood in general. To address these questions, 14 suggestion-prone healthy subjects rated reality of pain that was induced either by laser pulses to the skin or by hypnotic suggestion during functional MRI. Both pain states were associated with activation of the brain's pain circuitry. During laser stimulation, the sensory parts of this circuitry were activated more strongly, and their activation strengths correlated positively with the SRP. During suggestion-induced pain, the reality estimates were lower and correlated positively with activation strengths in the rostral and perigenual anterior cingulate cortex and in the pericingulate regions of the medial prefrontal cortex; a similar trend was evident during laser-induced pain. These findings support the view that information about sensory-discriminative characteristics of pain contributes to the SRP. Differences in such information between physically and psychologically induced pain, however, could be quantitative rather than qualitative and therefore insufficient for judging the reality of pain without knowledge about the source of this information. The medial prefrontal cortex is a likely area to contribute to such source monitoring.
Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: Implications for cancer immunotherapy
Authors: Friedman Lilach M. , Rinon Ariel , Schechter Bilha , Lyass Ljuba , Lavi Sara , Bacus Sarah S. , Sela Michael , Yarden Yosef
Published: February 2005

mAbs to receptor tyrosine kinases such as EGF receptor/ErbB-1 and HER2/ErbB-2 inhibit the tumorigenic growth of certain cancer cells, but although recombinant versions of such Abs are already used in oncology wards, the mechanism underlying immunotherapy remains unknown. We report that anti-EGF receptor Abs promote a slow endocytic process distinct from the rapid EGF-induced receptor internalization. Combining mAbs that engage distinct epitopes significantly accelerates receptor degradation. In addition, mAb combinations are more effective than single Abs in inhibiting HER2 signaling
in vitro
and tumorigenesis in animals. We present a model attributing efficacy of immunotherapy to the size of Ab-receptor lattices formed at the cell surface, which dictates the rate of endocytic clearance and extent of signaling blockade.
ADP inhibits function of the ABC transporter cystic fibrosis transmembrane conductance regulator via its adenylate kinase activity
Authors: Randak Christoph O. , Welsh Michael J.
Published: February 2005

ADP interacts with the nucleotide-binding domains (NBDs) of the cystic fibrosis transmembrane conductance regulator (CFTR) to inhibit its Cl
-
channel activity. Because CFTR NBD2 has reversible adenylate kinase activity (ATP + AMP ⇆ ADP + ADP) that gates the channel, we asked whether ADP might inhibit current through this enzymatic activity. In adenylate kinases, binding of the two ADP molecules is cooperative. Consistent with this hypothesis, CFTR current inhibition showed positive cooperativity for ADP. We also found that ADP inhibition of current was attenuated when we prevented adenylate kinase activity with P
1
,P
5
-di(adenosine-5′) pentaphosphate. Additional studies suggested that adenylate kinase-dependent inhibition involved phosphotransfer between two nucleotide diphosphates. These data indicate that the adenylate kinase reaction at NBD2 contributed to the inhibitory effect of ADP. Finding that ADP inhibits function via an adenylate kinase activity also helps explain the earlier observation that mutations that disrupt adenylate kinase activity also disrupt ADP inhibition. Thus, the results reveal a previously unrecognized mechanism by which ADP inhibits an ABC transporter.
Increased hypothalamic GPR54 signaling: A potential mechanism for initiation of puberty in primates
Authors: Shahab Muhammad , Mastronardi Claudio , Seminara Stephanie B. , Crowley William F. , Ojeda Sergio R. , Plant Tony M.
Published: February 2005

To further study the role of GPR54 signaling in the onset of primate puberty, we used the monkey to examine the ability of kisspeptin-10 to elicit the release of gonadotropin-releasing hormone (GnRH) precociously, and we describe the expression of
GPR54
and
KiSS-1
in the hypothalamus during the peripubertal period. Agonadal juvenile male monkeys were implanted with a lateral cerebroventricular cannula and a jugular vein catheter. The responsiveness of the juvenile pituitary to endogenous GnRH release was heightened with a chronic pulsatile i.v. infusion of synthetic GnRH before kisspeptin-10 (112-121) injection. Intracerebroventricular (30 μg or 100 μg) or i.v. (100 μg) bolus injections of kisspeptin-10 elicited a robust GnRH discharge, as reflected by luteinizing hormone secretion, which was abolished by pretreatment with a GnRH-receptor antagonist. RNA was isolated from the hypothalamus of agonadal males before (juvenile) and after (pubertal) the pubertal resurgence of pulsatile GnRH release and from juvenile, early pubertal, and midpubertal ovary-intact females. KiSS-1 mRNA levels detected by real-time PCR increased with puberty in both male and female monkeys. In intact females, but not in agonadal males, GPR54 mRNA levels in the hypothalamus increased ≈3-fold from the juvenile to midpubertal stage. Hybridization histochemistry indicated robust KiSS-1 and GPR54 mRNA expression in the region of the arcuate nucleus. These findings are consistent with the hypothesis that GPR54 signaling by its cognate ligand in the primate hypothalamus may be activated at the end of the juvenile phase of development and may contribute to the pubertal resurgence of pulsatile GnRH release, the central drive for puberty.
Syndromic patent ductus arteriosus: Evidence for haploinsufficientTFAP2Bmutations and identification of a linked sleep disorder
Authors: Mani Arya , Radhakrishnan Jayaram , Farhi Anita , Carew Khary S. , Warnes Carole A. , Nelson-Williams Carol , Day Ronald W. , Pober Barbara , State Matthew W. , Lifton Richard P.
Published: February 2005

Patent ductus arteriosus (PDA) is a common congenital heart disease that results when the ductus arteriosus, a muscular artery, fails to remodel and close after birth. A syndromic form of this disorder, Char syndrome, is caused by mutation inTFAP2B, the gene encoding a neural crest-derived transcription factor. Established features of the syndrome are PDA, facial dysmorphology, and fifth-finger clinodactyly. Disease-causing mutations are missense and are proposed to be dominant negative. Because only a small number of families have been reported, there is limited information on the spectrum of mutations and resulting phenotypes. We report the characterization of two kindreds (K144 and K145) with Char syndrome containing 22 and 5 affected members, respectively. Genotyping revealed linkage toTFAP2Bin both families. Sequencing ofTFAP2Bdemonstrated mutations in both kindreds that were not found among control chromosomes. Both mutations altered highly conserved bases in introns required for normal splicing as demonstrated by biochemical studies in mammalian cells. The abnormal splicing results in mRNAs containing frameshift mutations that are expected to be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency; even if produced, the protein in K144 would lack DNA binding and dimerization motifs and would likely result in haploinsufficiency. Examination of these two kindreds for phenotypes that segregate withTFAP2Bmutations identified several phenotypes not previously linked to Char syndrome. These include parasomnia and dental and occipital-bone abnormalities. The striking sleep disorder in these kindreds implicates TFAP2B-dependent functions in the normal regulation of sleep.
Bold, reckless and adaptable? Explaining gender differences in economic thinking and attitudes
Authors: Davies Peter , Mangan Jean , Telhaj Shqiponja
Published: February 2005

In the first half of this paper we develop a perspective on the role of ‘boldness’ in explaining gender differences in thinking and attitudes. We apply this analysis to evidence from Australia, the USA and the UK in relation to economics at school and university levels. In the second half we present the results of a study of over 1000 15–17‐year‐olds in UK secondary schools. On the basis of the gender differences revealed in these data and our preceding analysis we offer some implications for learning and teaching.
Job Guarantees, Employability Training and Partnerships in the Retail Sector
Authors: McQuaid Ronald W. , Lindsay Colin , Greig Malcolm
Published: February 2005

This paper discusses the potential value of local, partnership-based employability training and job guarantee programmes, focusing on one example—the ‘Alloa Initiative’. The Initiative involved an employability training and job guarantee scheme developed in partnership with Tesco, a major retailer, in preparation for the opening of one of the company's new stores. This paper reports on the outputs from this project, which placed 109 disadvantaged job seekers into positions at the store, and proved particularly effective at targeting the long-term unemployed and those with limited experience of the retail sector. The analysis is based on the findings of survey research undertaken with 86 of the 109 training course completers (a 79 per cent response rate) and all the main partners involved in the Initiative. Innovative elements of the training programme that contributed to its positive outcomes are discussed, and a model for ‘managing successful partnerships’ is applied, in order to identify critical factors explaining the apparent success of the Initiative. In particular, the importance of employers providing job guarantees is noted.
LSP1 is an endothelial gatekeeper of leukocyte transendothelial migration
Authors: Liu Lixin , Cara Denise C. , Kaur Jaswinder , Raharjo Eko , Mullaly Sarah C. , Jongstra-Bilen Jenny , Jongstra Jan , Kubes Paul
Published: February 2005

Leukocyte-specific protein 1 (LSP1), an F-actin binding protein and a major downstream substrate of p38 mitogen-activated protein kinase as well as protein kinase C, has been reported to be important in leukocyte chemotaxis. Although its distribution has been thought to be restricted to leukocytes, herein we report that LSP1 is expressed in endothelium and is essential to permit neutrophil emigration. Using intravital microscopy to directly visualize leukocyte rolling, adhesion, and emigration in postcapillary venules in LSP1-deficient (Lsp1−/−) mice, we found that LSP1 deficiency inhibits neutrophil extravasation in response to various cytokines (tumor necrosis factor-α and interleukin-1β) and to neutrophil chemokine keratinocyte-derived chemokine in vivo. LSP1 deficiency did not affect leukocyte rolling or adhesion. Generation of Lsp1−/− chimeric mice using bone marrow transplantation revealed that in mice with Lsp1−/− endothelial cells and wild-type leukocytes, neutrophil transendothelial migration out of postcapillary venules is markedly restricted. In contrast, Lsp1−/− neutrophils in wild-type mice were able to extravasate normally. Consistent with altered endothelial function was a reduction in vascular permeability to histamine in Lsp1−/− animals. Western blot analysis and immunofluorescence microscopy examination confirmed the presence of LSP1 in wild-type but not in Lsp1−/− mouse microvascular endothelial cells. Cultured human endothelial cells also stained positive for LSP1. Our results suggest that LSP1 expressed in endothelium regulates neutrophil transendothelial migration.
An Absolute Determination of Resistance Based on a Calculable Standard of Capacitance
Authors: A M Thompson
Published: February 2005

A determination of the NSL unit of resistance based on standards of length and frequency has been made. A cylindrical cross-capacitor, for which the change in capacitance for a measured change in length may be calculated very precisely, is used to calibrate a number of small fixed capacitors (1/6 or 1/4 pF). AC bridge techniques are used to build up to 10 nF and also to measure the resistance of a 10 kΩ resistor in terms of this capacitance and a measured frequency (ω = 104). DC measurements are used to relate the 10 kΩ resistor to the Laboratory's 1 Ω standard resistors.

The estimated uncertainty in the measurements is 2 in 107but the accuracy of the determination is limited to ± 7 in 107because of the uncertainty in the speed of light. Mean values, derived from a number of determinations, and corresponding to the times of the BIPM international comparisons, are

Jan. 1964ΩNSL= 1 Ω - 3.58 μΩFeb. 1967ΩNSL= 1 Ω - 3.80 μΩ.

The standard deviation of a series of determinations was 0.06 μΩ.
Tolerance for inequity may increase with social closeness in chimpanzees
Authors: Brosnan Sarah F. , Schiff Hillary C. , de Waal Frans B. M.
Published: February 2005

Economic decision–making depends on our social environment. Humans tend to respond differently to inequity in close relationships, yet we know little about the potential for such variation in other species. We examine responses to inequity in several groups of chimpanzees (Pan troglodytes) in a paradigm similar to that used previously in capuchin monkeys (Cebus apella). We demonstrate that, like capuchin monkeys, chimpanzees show a response to inequity of rewards that is based upon the partner receiving the reward rather than the presence of the reward alone. However, we also found a great amount of variation between groups tested, indicating that chimpanzees, like people, respond to inequity in a variable manner, which we speculate could be caused by such variables as group size, the social closeness of the group (as reflected in length of time that the group has been together) and group–specific traditions.
Hic-5 regulates an epithelial program mediated by PPARγ
Authors: Drori Stavit , Girnun Geoffrey D. , Tou Liqiang , Szwaya Jeffrey D. , Mueller Elisabetta , Kia Xia , Shivdasani Ramesh A. , Spiegelman Bruce M.
Published: February 2005

PPARγ is a dominant regulator of fat cell differentiation. However, this nuclear receptor also plays an important role in the differentiation of intestinal and other epithelial cell types. The mechanism by which PPARγ can influence the differentiation of such diverse cell lineages is unknown. We show here that PPARγ interacts with Hic-5, a coactivator protein expressed in gut epithelial cells. Hic-5 and PPARγ colocalize to the villus epithelium of the small intestine, and their expression during embryonic gut development correlates with the transition from endoderm to a specialized epithelium; expression of both these factors is reduced in tumors. Forced expression of Hic-5 in colon cancer cells enhances the PPARγ-mediated induction of several gut epithelial differentiation/maturation markers such as L-FABP, kruppel-like factor 4 (KLF4), and keratin 20. siRNA directed against Hic-5 specifically reduces PPARγ-mediated induction of gut epithelial genes in colon cells and in an ex vivo model of embryonic gut differentiation. Finally, forced expression of Hic-5 during 3T3-L1 preadipocyte differentiation inhibits adipogenesis while inducing inappropriate expression of several mRNAs characteristic of gut epithelium in these mesenchymal cells. These results indicate that Hic5 is an important component in determining an epithelial differentiation program induced by PPARγ.