bluuebunny/crossref_metadata_2025 huggingface dataset:
Mohs '98: Single‐Procedure Mohs Surgery with Immediate Reconstruction
Authors: BERNSTEIN PAUL E.
Published: November 2005

For more than 50 years, the Mohs technique has offered both the highest cure rate for skin cancers and the maximum preservation of surrounding normal tissue. Mohs skin cancer excision is traditionally performed by a Mohs dermatologist, followed by a secondary repair by a head and neck or plastic surgeon. This study comprises a review of 300 cases involving single‐procedure Mohs therapy with immediate one‐anesthetic reconstruction. The data reviewed include types of reconstructions, cosmetic results, complications, and recurrence rates. In addition to offering the psychologic and quality advantages of immediate closure, the procedure allows patients to return to work sooner. With changes in technique ranging from the chemosurgery of the 1930s to the fresh‐tissue methods of the 1970s, single‐procedure Mohs is the logical next step in the evolution of Mohs surgery.
Percutaneous Endoscopic Gastrostomy: Avoiding Complications
Authors: SANTOS PERRY M. , McDONALD JAMES
Published: November 2005

This study evaluates our complications arising directly or indirectly from placement or management of percutaneous endoscopic gastrostomy (PEG) tubes and provides recommendations for avoidance of complications. Seventy‐one patients received PEG tube placement by otolaryngologists between January 1991 and May 1997. Records were reviewed for diagnoses, combined procedures, and complications. Addressing potential causes of complications prompted modification of our technique of PEG tube placement and management. Twenty‐three patients received PEG for dysphagia/aspiration unrelated to neoplasia, 11 received PEG with staging endoscopy, 11 received PEG after treatment for head and neck neoplasm, and 26 received PEG at the time of primary resection. Major complications included retained PEG hub and delayed colon abscess ultimately resulting in death. Minor complications included skin abscesses, cellulitis, and early and late vasovagal response with PEG tube removal. An airway emergency, on attempted oral airway intubation, resulted in an aborted PEG attempt and constituted another complication outside the 4 groups stated above. The major complication was not found within a literature review. We have modified our management for avoidance of this complication. We believe the causes of the minor complications have been identified, and with additional modifications in our technique, we have not had any similar complications recently. The recommended techniques are discussed in detail.
Cyclin D1 Expression as a Prognostic Parameter in Papillary Carcinoma of the Thyroid
Authors: MURO‐CACHO CARLOS A. , HOLT THOMAS , KLOTCH DOUGLAS , MORA LINDA , LIVINGSTON SANDRA , FUTRAN NEIL
Published: November 2005

Papillary carcinoma of the thyroid is the most common thyroid cancer. At the time of clinical presentation, most papillary carcinomas are still confined to the thyroid gland, and appropriate surgical treatment achieves a 95% 5‐year survival rate. Certain carcinomas, however, behave in a much more aggressive fashion. Because specific therapies do not exist, for those tumors that have escaped local control, patients with disseminated disease have little or no chance of permanent cure or long‐term survival. Cyclin D1, a protein that plays a critical role in the control of the cell cycle, has been shown to be overexpressed in a variety of human neo‐plasias and may serve as a prognostic parameter of disease progression. To explore the role played by cyclin D1 in the pathogenesis of thyroid papillary carcinoma, we have quantitated, by computerized image analysis, the immunohistochemical expression of cyclin D1 in formalin‐fixed, paraffin‐embedded tissue from 35 conventional papillary carcinomas of the thyroid and correlated the results with established clinicopathologic parameters and available survival data.
Role of Gastroesophageal Reflux in Pediatric Upper Airway Disorders
Authors: HALSTEAD LUCINDA A.
Published: November 2005

Gastroesophageal reflux (GER) into the laryngopharynx causes or contributes significantly to a variety of upper respiratory problems in children. The pH probe, laryngeal examinations, and bron‐choalveolar lavage results for children with subglottic stenosis, recurrent croup, apnea, chronic cough, laryngomalacia, recurrent choanal stenosis, vocal fold nodules, and chronic sinusitis/otitis/bronchitis were reviewed in an effort to quantify the role of GER in each of these disorders. This review suggests that GER plays a causative role in subglottic stenosis, recurrent croup, apnea, and chronic cough. It is an important inflammatory cofactor in laryngoma‐lacia and possibly in true vocal cord nodules and problematic recurrent choanal stenosis. GER is also an important inflammatory cofactor in chronic sinusitis/otitis/bronchitis but may be the result of chronic illness in the older patients.
Learning Curve in Endoscopic Sinus Surgery
Authors: MARKS STEVEN C.
Published: November 2005

The existence of a long learning curve for endo‐scopic sinus surgery has been proposed as a reason for rigorous and extensive training to prepare physicians to perform this surgery. In this article, the author—who participated in this type of training program—examines his experience over a 5‐year period to assess the effect of rigorous training on the learning curve for endoscopic sinus surgery. Beginning with the first day of practice after training, 5 years with 393 cases were evaluated for complications and the need for revision surgery. The results were analyzed in 100‐case groups. The results show no difference in major and serious complications or revision surgery rates. However, a statistically significant difference in the minor‐complication rate, specifically frontal‐sinus stenosis, was found from the first half to the second half of the experience. These findings show that, with rigorous training of the physician, the learning curve can largely be completed during residency training, allowing the new practitioner to perform endoscopic sinus surgery safely and with good results.
Obstructive Sleep Apnea in Children with Achondroplasia: Surgical and Anesthetic Considerations
Authors: SISK ELIZABETH A. , HEATLEY DIANE G. , BOROWSKI BRET J. , LEVERSON GLEN E. , PAULI RICHARD M.
Published: November 2005

OBJECTIVE

To evaluate the prevalence of obstructive sleep apnea in a large population of children with achondroplasia and to evaluate the effectiveness of adenoidectomy and/or tonsillectomy as treatment.

METHODS

Retrospective review of 95 children with achondroplasia.

RESULTS

Thirty‐six patients (38%) had clinical evidence of obstructive sleep apnea. Thirty‐four patients underwent surgery, with more than 1 procedure required in 10 children (29%). Adenotonsil‐lectomy was the initial procedure for 22 of 34 patients, and further therapy was required in only 18% of this group. Adenoidectomy was the initial procedure for 10 of 34, with 90% requiring further surgery for recurrent obstructive sleep apnea. Tonsillectomy alone was performed in 2 patients: 1 was effectively treated and 1 later required adenoidectomy. Endotracheal intubation was accomplished in all patients without complication; 53% required a smaller endotracheal tube than would be predicted by their age. Eight postoperative complications were recorded.

CONCLUSIONS

Obstructive sleep apnea is very common in children with achondroplasia. Surgery is effective, but recurrent symptoms are common, particularly when the initial procedure is adenoidectomy. The complication rate is higher than that observed in a general pediatric population but is readily managed with standard therapy. Anesthesia can be given safely to these patients with special consideration for limited neck extension and appropriate endotracheal tube size.
Effects of Estrogen and Tamoxifen on Growth of Human Vestibular Schwannomas in the Nude Mouse
Authors: STIDHAM KATRINA R. , ROBERSON JOSEPH B.
Published: November 2005

Vestibular schwannomas have been noted to have increased frequency and aggressivity in female patients, suggesting a possible role of estrogen. This study evaluated the effects of estrogen and tamoxifen on the growth of human vestibular schwannoma tissue implanted in subcutaneous pockets of nude mice. Animals were implanted with 1 of 3 human vestibular schwannomas and observed for 28 days. Mice were then separated into 3 treatment groups: controls, estrogen (receiving 1.7 mg of 17B‐estradiol), and estrogen + tamoxifen (receiving 1.7 mg of 17B‐estradiol + 10 mg of tamoxifen), and treated for 28 days. Mice treated with estrogen showed increased growth that was statistically significant (P < 0.05) when compared with that of both the controls and the animals treated with estrogen + tamoxifen. Controls and animals treated with estrogen + tamoxifen showed a general trend of decreased volume during the treatment period. These early results support the hypothesis that estrogen modulates the growth of vestibular schwannomas in the nude mouse model and that these effects can be blocked by tamoxifen administration.
Medialization Laryngoplasty
Authors: DULGUEROV PAVEL , SCHWEIZER VAL$EARIE , CAUMEL ISABELLE , ESTEVE FRAN$CLOISE
Published: November 2005

Medialization laryngoplasty was performed in 25 patients between 1993 and 1997. The underlying pathology resulting in glottal incompetence was vocal cord paralysis in 22 patients and vocal cord bowing in 3 patients. Two types of implants were used: self‐carved Proplast in 19 patients and prefabricated hydroxyapatite prostheses in 6 patients. Preoperative and postoperative results were compared in terms of dysphagia, vocal quality as graded by three experienced voice specialists, and computer measurements of the glottal gap. All patients showed improvement both subjectively and on the objective measurements used. Swallowing returned to normal in all patients who had isolated recurrent laryngeal nerve paralysis. The voice improved in all patients but was rarely judged as entirely normal.
Effects of the 1997–1998 El Niño on the exchange of the northern Gulf of California
Authors: López Manuel , Zamudio Luis , Padilla Francisco
Published: November 2005

We analyze sea level and transports in the Gulf of California from two large‐scale, high‐resolution numerical models: the Naval Research Laboratory Layered Ocean Model and the Hybrid Coordinate Ocean Model. Sea level from both models correlates well with sea surface height from a nearby TOPEX track and subsurface pressure measured in the northern gulf during 1997–1998. An 8‐year mean (1993–2000) section of the modeled meridional velocity at the mouth of the gulf is in good qualitative agreement with observations, showing a localized near‐surface outflow on the Baja California side. The 8‐year mean, laterally integrated modeled near‐surface transport at the mouth of the gulf shows an opposite direction for both models. During the 1997–1998 El Niño, however, both models show a similar structure with increased inflow in the upper 100 m and an increased outflow in the underlying layer to about 500 m depth. The modeled surface transport also shows increased inflow in the northern gulf. The modeled incoming surface transport from both models during El Niño is negatively correlated to near‐bottom currents measured at a sill in the northern gulf. This measured near‐bottom current has previously been shown to constitute part of the strong, localized incoming flow from the Pacific Ocean. The negative correlation strongly suggests that the anomalous incoming surface flow at the mouth of the gulf inhibited the normal near‐surface outflow of the northern Gulf of California water. This, in turn, inhibited the normal deeper inflow, entering the northern gulf from the Pacific Ocean. These anomalies apparently increased the residence time of the waters in the northern gulf. They are consistent with anomalously high near‐bottom salinities found during 1997–1998. Hydrographic data for July 1997 also show an anomalous low salinity surface water, which is most likely associated with advection of tropical waters from the Pacific Ocean.
A modeling study of the response of tropical deep convection to the increase of cloud condensation nuclei concentration: 1. Dynamics and microphysics
Authors: Wang Chien
Published: November 2005

The responses of cloud physical processes of a developing tropical deep convection to the increase of CCN concentration have been studied using a three‐dimensional cloud‐resolving model. Three sets of model simulations, each consisting of 30 runs initialized using a set of 30 different CCN profiles with maximum concentrations ranging from 50 to 6000/cm3, have been carried out. The finding of this study that cloud droplet number concentration increases while cloud droplet size decreases with aerosol concentration is similar to the previous results mainly revealed in studies of stratiform clouds. However, the responses to increasing aerosol concentration of many other cloud properties illustrated in this study, particularly precipitation, are very different from those found or suggested in studies of stratiform clouds. Increasing CCN concentration causes a stronger convection, added mass of condensed water, and enhanced microphysical conversions, all leading to the increase in precipitation as well as the expansion of the cloud coverage. Interestingly, when initial CCN concentration exceeds a certain level, many of the above effects become insignificant, suggesting a relationship between some cloud properties and the logarithm of CCN concentration and further implying that a more substantial aerosol effect on deep convection could be seen over a clean rather than polluted region. Overall speaking, increasing CCN concentration does not significantly affect the precipitation efficiency. The increase with CCN concentration of upward flux of water vapor entering the cloud thus leads to an enhancement in moistening the free troposphere brought by the modeled cloud, besides adding more precipitation to the ground.
Optical, physical, and chemical properties of tar balls observed during the Yosemite Aerosol Characterization Study
Authors: Hand J. L. , Malm W. C. , Laskin A. , Day D. , Lee T. , Wang C. , Carrico C. , Carrillo J. , Cowin J. P. , Collett J. , Iedema M. J.
Published: November 2005

The Yosemite Aerosol Characterization Study of summer 2002 (YACS) occurred during an active fire season in the western United States and provided an opportunity to investigate many unresolved issues related to the radiative effects of biomass burning aerosols. Single particle analysis was performed on field‐collected aerosol samples using an array of electron microscopy techniques. Amorphous carbon spheres, or “tar balls,” were present in samples collected during episodes of high particle light scattering coefficients that occurred during the peak of a smoke/haze event. The highest concentrations of light‐absorbing carbon from a dual‐wavelength aethalometer (λ = 370 and 880 nm) occurred during periods when the particles were predominantly tar balls, indicating they do absorb light in the UV and near‐IR range of the solar spectrum. Closure experiments of mass concentrations and light scattering coefficients during periods dominated by tar balls did not require any distinct assumptions of organic carbon molecular weight correction factors, density, or refractive index compared to periods dominated by other types of organic carbon aerosols. Measurements of the hygroscopic behavior of tar balls using an environmental SEM indicate that tar balls do not exhibit deliquescence but do uptake some water at high (∼83%) relative humidity. The ability of tar balls to efficiently scatter and absorb light and to absorb water has important implications for their role in regional haze and climate forcing.
Miniaturization of electromagnetic band gap structures for mobile applications
Authors: Goussetis G. , Feresidis A. P. , Palikaras G. K. , Kitra M. , Vardaxoglou J. C.
Published: November 2005

It is well known that interference of the human body affects the performance of the antennas in mobile phone handsets. In this contribution, we investigate the use of miniaturized metallodielectric electromagnetic band gap (MEBG) structures embedded in the case of a mobile handset as a means of decoupling the antenna from the user's hand. The closely coupled MEBG concept is employed to achieve miniaturization of the order of 15:1. Full wave dispersion relations for planar closely coupled MEBG arrays are presented and are validated experimentally. The performance of a prototype handset with an embedded conformal MEBG is assessed experimentally and is compared to a similar prototype without the MEBG. Reduction in the detuning of the antenna because of the human hand by virtue of the MEBG is demonstrated. Moreover, the efficiency of the handset when loaded with a human hand model is shown to improve when the MEBG is in place. The improvements are attributed to the decoupling of the antenna from the user's hand, which is achieved by means of suppressing the fields in the locality of the hand.
Interannual variability in North American grassland biomass/productivity detected by SeaWinds scatterometer backscatter
Authors: Frolking S. , Fahnestock M. , Milliman T. , McDonald K. , Kimball J.
Published: November 2005

We analyzed 2000–2004 growing‐season SeaWinds Ku‐band microwave backscatter and MODIS leaf area index (LAI) data over North America. Large anomalies in mid‐growing‐season mean backscatter and LAI, relative to 5‐year mean values, occurred primarily in the western Great Plains; backscatter and LAI anomalies had similar spatial patterns across this region. Backscatter and LAI time series data for three ∼103 km2 regions in the western Great Plains were strongly correlated (r2 ∼ 0.6–0.8), and variability in mid‐growing season values was well‐correlated with annual precipitation (October through September). The results indicate that SeaWinds backscatter is sensitive to interannual variability in grassland biomass/productivity, and can provide an assessment that is completely independent of optical/near‐infrared remote sensing instruments.
Specific absorption cross‐section and elemental carbon content of urban aerosols
Authors: Chou Charles C.‐K. , Chen Wei‐Nai , Chang Shih‐Yu , Chen Tze‐Kuang , Huang Shu‐Hui
Published: November 2005

To investigate the light absorption efficiency of aerosols, samples of fine particulate matter (PM2.5) were collected during a field experiment in Taipei, Taiwan. Mass concentration and the elemental carbon (EC) content of the PM2.5 samples were measured, and in addition the light absorption cross‐section of the EC in PM2.5 was derived. On average, elemental carbon contributed 8.6 ± 3.5 % to the PM2.5 mass. The aerosol light absorption coefficient was linearly proportional to the ambient EC concentration. Consequently, an average specific absorption cross‐section of 10.8 ± 2.6 m2/g was obtained for EC in the aerosols. Analyses of the variations in the absorption cross‐section revealed that the cross‐section converged towards the average level as the ambient EC concentration increased. The scattering in the low EC regime is proposed to be due to differences in the mixing state: internal mixing enhanced the cross‐section, whereas external mixing resulted in a decreasing trend.
Impact of high‐frequency waves on the ocean altimeter range bias
Authors: Vandemark D. , Chapron B. , Elfouhaily T. , Campbell J. W.
Published: November 2005

New aircraft observations are presented on the range determination error in satellite altimetry associated with ocean waves. Laser‐based measurements of the cross correlation between the gravity wave slope and elevation are reported for the first time. These observations provide direct access to a long, O(10 m), gravity wave statistic central to nonlinear wave theory prediction of the altimeter sea state bias. Coincident Ka‐band radar scattering data are used to estimate an electromagnetic (EM) range bias analogous to that in satellite altimetry. These data, along with ancillary wind and wave slope variance estimates, are used alongside existing theory to evaluate the extent of long‐ versus short‐wave, O(cm), control of the bias. The longer wave bias contribution to the total EM bias is shown to range from 25 to as much as 100%. Moreover, on average the term is linearly related to wind speed and to the gravity wave slope variance, consistent with WNL theory. The EM bias associated with interactions between long and short waves is obtained assuming the effect is additive to the independently observed long‐wave factor. This second component is also a substantial contributor, is observed to be quadratic in wind speed or wave slope, and dominates at moderate wind speeds. The behavior is shown to be consistent with EM bias prediction based in hydrodynamic modulation theory. Study implications for improved correction of the on‐orbit satellite sea state bias are discussed.
Growth rates of freshly nucleated atmospheric particles in Atlanta
Authors: Stolzenburg Mark R. , McMurry Peter H. , Sakurai Hiromu , Smith James N. , Mauldin R. Lee , Eisele Fred L. , Clement Charles F.
Published: November 2005

During the Atlanta ANARChE Study of July and August 2002, atmospheric aerosol size distributions from 3 to 2000 nm were measured continuously with 5‐min resolution. Sulfuric acid vapor concentrations were also measured. During regional nucleation events these data showed the presence of a nucleation mode that grew at rates ranging from 3 to 20 nm h−1. In this paper we compare these measured modal growth rates with calculated rates that account for sulfuric acid condensation, intramodal coagulation of nucleation mode particles, and extramodal coagulation of nucleation mode particles with preexisting particles. Data collected during six time intervals were amenable to analysis. Calculated and measured growth rates were in reasonable agreement for the four events that involved growth below 40 nm (ratios of measured to calculated growth rates = 1.0, 2.1, 0.68, 0.60). Two of the three afternoon events involved growth above 40 nm, and in these cases, measured rates substantially exceeded calculated rates by factors of four to five, suggesting that our model did not account for all growth processes. We also compared observed rates of change in nucleation mode number concentration with calculated coagulation rates during these six time intervals. During the sub‐40 nm growth events, particle concentrations changed at rates that were significantly below calculated coagulation rates. In two of these cases, particle concentrations increased during the growth period, suggesting that a source of particles was present. Measured size distributions suggest that particle production by nucleation continued during these events and contributed to this discrepancy. Concentrations during the super‐40 nm events decreased at rates that exceeded calculated coagulation rates.
Extensive dust outbreaks following the morning inversion breakup in the Taklimakan Desert
Authors: Tsunematsu Nobumitsu , Sato Tomonori , Kimura Fujio , Kai Kenji , Kurosaki Yasunori , Nagai Tomohiro , Zhou Hongfei , Mikami Masao
Published: November 2005

Extensive dust outbreaks occurred on the late morning of 26 March 2004 in the Taklimakan Desert. An image by the satellite AQUA shows the dust outbreaks as an enormous dust storm extending as far as 1000 km in the direction of east and west across the desert. A ground‐based lidar was successful in observing the dust storm. Values of the backscattering ratio from near the ground surface to an altitude of 6 km above sea level rapidly increased as soon as the dust storm covered the lidar observation site. Numerical experiments including a diffusion experiment revealed that strong westerly winds appeared at the surface level following the morning inversion breakup and then induced the dust outbreaks. The nocturnal inversion layer prevented the strong westerly winds from spreading to the surface level until the breakup. Notable nocturnal inversion is considered to be easily formed in the Taklimakan Desert because of its deep basin topography which can accumulate cold air masses. These results show the stability of the planetary boundary layer to be an extremely important factor in dust outbreaks especially in basin deserts, in addition to the intensity of surface winds. This implies that the occurrence frequency of dust storms in the desert has a diurnal cycle.
Heat-shock cognate 70 is required for the activation of heat-shock factor 1 in mammalian cells
Authors: Ahn Sang-Gun , Kim Soo-A , Yoon Jung-Hoon , Vacratsis Panayiotis
Published: November 2005

HSF1 (heat-shock factor 1) plays an essential role in mediating the appropriate cellular response to diverse forms of physiological stresses. However, it is not clear how HSF1 is regulated by interacting proteins under normal and stressful conditions. In the present study, Hsc70 (heat-shock cognate 70) was identified as a HSF1-interacting protein using the TAP (tandem affinity purification) system and MS. HSF1 can interact with Hsc70 in vivo and directly in vitro. Interestingly, Hsc70 is required for the regulation of HSF1 during heat stress and subsequent target gene expression in mammalian cells. Moreover, cells transfected with siRNAs (small interfering RNAs) targeted to Hsc70 showed greatly decreased HSF1 activation with expression of HSF1 target genes being dramatically reduced. Finally, loss of Hsc70 expression in cells resulted in an increase in stress-induced apoptosis. These results indicate that Hsc70 is a necessary and critical regulator of HSF1 activities.
A large displacement of the SXN motif of Cys115-modified penicillin-binding protein 5 from Escherichia coli
Authors: Nicola George , Fedarovich Alena , Nicholas Robert A. , Davies Christopher
Published: November 2005

Penicillin-binding proteins (PBPs), which are the lethal targets of β-lactam antibiotics, catalyse the final stages of peptidoglycan biosynthesis of the bacterial cell wall. PBP 5 of Escherichia coli is a D-alanine CPase (carboxypeptidase) that has served as a useful model to elucidate the catalytic mechanism of low-molecular-mass PBPs. Previous studies have shown that modification of Cys115 with a variety of reagents results in a loss of CPase activity and a large decrease in the rate of deacylation of the penicilloyl–PBP 5 complex [Tamura, Imae and Strominger (1976) J. Biol. Chem. 251, 414–423; Curtis and Strominger (1978) J. Biol. Chem. 253, 2584–2588]. The crystal structure of wild-type PBP 5 in which Cys115 fortuitously had formed a covalent adduct with 2-mercaptoethanol was solved at 2.0 Å (0.2 nm) resolution, and these results provide a structural rationale for how thiol-directed reagents lower the rate of deacylation. When compared with the structure of the unmodified wild-type enzyme, a major change in the architecture of the active site is observed. The two largest differences are the disordering of a loop comprising residues 74–90 and a shift in residues 106–111, which results in the displacement of Ser110 of the SXN active-site motif. These results support the developing hypothesis that the SXN motif of PBP 5, and especially Ser110, is intimately involved in the catalytic mechanism of deacylation.
Human T-cell lymphotropic virus type I-transformed T-cells have a partial defect in ceramide synthesis in response to N-(4-hydroxyphenyl)retinamide
Authors: Darwiche Nadine , Abou-Lteif Ghada , Najdi Tarek , Kozhaya Lina , Abou Tayyoun Ahmad , Bazarbachi Ali , Dbaibo Ghassan S.
Published: November 2005

Treatment with the synthetic retinoid HPR [N-(4-hydroxyphenyl)-retinamide] causes growth arrest and apoptosis in HTLV-I (human T-cell lymphotropic virus type-I)-positive and HTLV-I-negative malignant T-cells [8]. It was observed that HPR-mediated growth inhibition was associated with ceramide accumulation only in HTLV-I-negative cells. The aim of the present study was to investigate the mechanism by which HPR differentially regulates ceramide metabolism in HTLV-I-negative and HTLV-I-positive malignant T-cells. Clinically achievable concentrations of HPR caused early dose-dependent increases in ceramide levels only in HTLV-I-negative cells and preceded HPR-induced growth suppression. HPR induced de novo synthesis of ceramide in HTLV-I-negative, but not in HTLV-I-positive, cells. Blocking ceramide glucosylation in HTLV-I-positive cells, which leads to accumulation of endogenous ceramide, rendered these cells more sensitive to HPR. Exogenous cell-permeant ceramides that function partially by generating endogenous ceramide induced growth suppression in all tested malignant lymphocytes, were consistently found to be less effective in HTLV-I-positive cells confirming their defect in de novo ceramide synthesis. Owing to its multipotent activities, the HTLV-I-encoded Tax protein was suspected to inhibit ceramide synthesis. Tax-transfected Molt-4 and HELA cells were less sensitive to HPR and C6-ceramide mediated growth inhibition respectively and produced lower levels of endogenous ceramide. Together, these results indicate that HTLV-I-positive cells are defective in de novo synthesis of ceramide and that therapeutic modalities that bypass this defect are more likely to be successful.
Increase in cell-surface localization of parathyroid hormone receptor by cytoskeletal protein 4.1G
Authors: Saito Masaki , Sugai Maki , Katsushima Yuriko , Yanagisawa Teruyuki , Sukegawa Jun , Nakahata Norimichi
Published: November 2005

The cell-surface localization of GPCRs (G-protein-coupled receptors) has emerged as one of critical factors of the GPCR-mediated signal transduction. It has been reported that the C-termini of GPCRs contain the sequences for sorting the receptors to cell surface. In the present study, we have searched for proteins that interact with the C-terminus of PTH (parathyroid hormone)/PTH-related protein receptor (PTHR) by using the yeast two-hybrid system, and identified a cytoskeletal protein 4.1G (generaltype 4.1 protein) as an interactant with the C-terminus. Immunohistochemical study revealed that both PTHR and 4.1G were co-localized on plasma membranes, when they were transiently expressed in COS-7 cells. When 4.1G or the C-terminal domain of 4.1G (4.1G-CTD), a dominant-negative form of 4.1G, was co-expressed with PTHR in COS-7 cells, 4.1G, but not 4.1G-CTD, facilitated the cell-surface localization of PTHR, determined by cell-surface biotinylation assay. PTH-(1–34) caused phosphorylation of ERK (extracellular-signal-regulated kinase) 1/2 in PTHR-expressed cells mainly mediated through EGF (epidermal growth factor) receptor. The phosphorylation was enhanced by the expression of 4.1G, but not 4.1G-CTD. PTH-(1–34) elevated [Ca2+]i (intracellular Ca2+ concentration) independent of EGF receptor activation, and the elevation was enhanced by the expression of 4.1G, but not 4.1G-CTD. These data indicate that 4.1G facilitates the cell-surface localization of PTHR through its interaction with the C-terminus of the receptor, resulting in the potentiation of PTHR-mediated signal transduction.
A polycystin multiprotein complex constitutes a cholesterol-containing signalling microdomain in human kidney epithelia
Authors: Roitbak Tamara , Surviladze Zurab , Tikkanen Ritva , Wandinger-Ness Angela
Published: November 2005

Polycystins are plasma membrane proteins that are expressed in kidney epithelial cells and associated with the progression of ADPKD (autosomal dominant polycystic kidney disease). A polycystin multiprotein complex, including adherens junction proteins, is thought to play an important role in cell polarity and differentiation. Sucrose gradient analyses and immunoprecipitation studies of primary human kidney epithelial cells showed the polycystins and their associated proteins E-cadherin and β-catenin distributed in a complex with the raft marker flotillin-2, but not caveolin-1, in high-density gradient fractions. The integrity of the polycystin multiprotein complex was sensitive to cholesterol depletion, as shown by cyclodextrin treatment of immunoprecipitated complexes. The overexpressed C-terminus of polycystin-1 retained the ability to associate with flotillin-2. Flotillin-2 was found to contain CRAC (cholesterol recognition/interaction amino acid) cholesterol-binding domains and to promote plasma membrane cholesterol recruitment. Based on co-association of signalling molecules, such as Src kinases and phosphatases, we propose that the polycystin multiprotein complex is embedded in a cholesterol-containing signalling microdomain specified by flotillin-2, which is distinct from classical light-buoyant-density, detergent-resistant domains.
Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors
Authors: Yang Yu , Xiong Zeyu , Zhang Sheng , Yan Yan , Nguyen Justin , Ng Bernard , Lu Huifang , Brendese John , Yang Fan , Wang Hong , Yang Xiao-Feng
Published: November 2005

One of the hallmark findings in patients suffering from SARS (severe acute respiratory syndrome) is lymphopenia, which is the result of massive lymphocyte death. SARS-CoV (SARS coronavirus), a novel coronavirus that has been etiologically associated with SARS cases, is homologous with MHV (murine hepatitis coronavirus), and MHV small envelope E protein is capable of inducing apoptosis. We hypothesized that SARS-CoV encodes a small envelope E protein that is homologous with MHV E protein, thus inducing T-cell apoptosis. To test this hypothesis, a cDNA encoding SARS-CoV E protein was created using whole gene synthesis. Our results showed that SARS-CoV E protein induced apoptosis in the transfected Jurkat T-cells, which was amplified to higher apoptosis rates in the absence of growth factors. However, apoptosis was inhibited by overexpressed antiapoptotic protein Bcl-xL. Moreover, we found that SARS-CoV E protein interacted with Bcl-xL in vitro and endogenous Bcl-xL in vivo and that Bcl-xL interaction with SARS-CoV E protein was mediated by BH3 (Bcl-2 homology domain 3) of Bcl-xL. Finally, we identified a novel BH3-like region located in the C-terminal cytosolic domain of SARS-CoV E protein, which mediates its binding to Bcl-xL. These results demonstrate, for the first time, a novel molecular mechanism of T-cell apoptosis that contributes to the SARS-CoV-induced lymphopenia observed in most SARS patients.
AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes
Authors: Karchner Sibel I. , Franks Diana G. , Hahn Mark E.
Published: November 2005

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates gene expression following activation by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) or a variety of other synthetic and natural compounds. Previous studies have identified two AHR genes, AHR1 and AHR2, in zebrafish (Danio rerio), a widely used model species for studying vertebrate development and an emerging model in developmental toxicology. Zebrafish AHR2 binds TCDD with high affinity, is transcriptionally active and has a major role in mediating the developmental toxicity of TCDD. Zebrafish AHR1 lacks the ability to bind TCDD and activate transcription, and has no known function. In the present study, we report a new zebrafish AHR, designated AHR1B, which shares 34% amino acid sequence identity with AHR1 (AHR1A). The ahr1b gene resides on chromosome 22, adjacent to ahr2, whereas the ahr1a gene is located on chromosome 16. AHR1B is expressed in embryos as early as 24 hours post-fertilization and increases through the next 2 days, but expression is not inducible by TCDD. In contrast with the previously identified AHR1A, in vitro-expressed AHR1B protein exhibits specific, high-affinity binding of [3H]TCDD. Furthermore, AHR1B is able to activate the transcription of a reporter gene under the control of AHR response elements with an efficacy comparable with that of AHR2, but with a higher EC50. We speculate that AHR1B may have a physiological role, such as in embryonic development, whereas AHR2 mediates the response to xenobiotics.
Phosphodiesterase 3A binds to 14-3-3 proteins in response to PMA-induced phosphorylation of Ser428
Authors: Pozuelo Rubio Mercedes , Campbell David G. , Morrice Nicholas A. , Mackintosh Carol
Published: November 2005

PDE3A (phosphodiesterase 3A) was identified as a phosphoprotein that co-immunoprecipitates with endogenous 14-3-3 proteins from HeLa cell extracts, and binds directly to 14-3-3 proteins in a phosphorylation-dependent manner. Among cellular stimuli tested, PMA promoted maximal binding of PDE3A to 14-3-3 proteins. While p42/p44 MAPK (mitogen-activated protein kinase), SAPK2 (stress-activated protein kinase 2)/p38 and PKC (protein kinase C) were all activated by PMA in HeLa cells, the PMA-induced binding of PDE3A to 14-3-3 proteins was inhibited by the non-specific PKC inhibitors Ro 318220 and H-7, but not by PD 184352, which inhibits MAPK activation, nor by SB 203580 and BIRB0796, which inhibit SAPK2 activation. Binding of PDE3A to 14-3-3 proteins was also blocked by the DNA replication inhibitors aphidicolin and mimosine, but the PDE3A–14-3-3 interaction was not cell-cycle-regulated. PDE3A isolated from cells was able to bind to 14-3-3 proteins after in vitro phosphorylation with PKC isoforms. Using MS/MS of IMAC (immobilized metal ion affinity chromatography)-enriched tryptic phosphopeptides and phosphospecific antibodies, at least five sites on PDE3A were found to be phosphorylated in vivo, of which Ser428 was selectively phosphorylated in response to PMA and dephosphorylated in cells treated with aphidicolin and mimosine. Phosphorylation of Ser428 therefore correlated with 14-3-3 binding to PDE3A. Ser312 of PDE3A was phosphorylated in an H-89-sensitive response to forskolin, indicative of phosphorylation by PKA (cAMP-dependent protein kinase), but phosphorylation at this site did not stimulate 14-3-3 binding. Thus 14-3-3 proteins can discriminate between sites in a region of multisite phosphorylation on PDE3A. An additional observation was that the cytoskeletal cross-linker protein plectin-1 coimmunoprecipitated with PDE3A independently of 14-3-3 binding.
Crystal structure of wild-type human thrombin in the Na+-free state
Authors: Johnson Daniel J. D. , Adams Ty E. , Li Wei , Huntington James A.
Published: November 2005

Regulation of thrombin activity is critical for haemostasis and the prevention of thrombosis. Thrombin has several procoagulant substrates, including fibrinogen and platelet receptors, and essential cofactors for stimulating its own formation. However, thrombin is also capable of serving an anticoagulant function by activating protein C. The specificity of thrombin is primarily regulated by binding to the cofactor TM (thrombomodulin), but co-ordination of Na+ can also affect thrombin activity. The Na+-free form is often referred to as ‘slow’ because of reduced rates of cleavage of procoagulant substrates, but the slow form is still capable of rapid activation of protein C in the presence of TM. The molecular basis of the slow proteolytic activity of thrombin has remained elusive, in spite of two decades of solution studies and many published crystallographic structures. In the present paper, we report the first structure of wild-type unliganded human thrombin grown in the absence of co-ordinating Na+. The Na+-binding site is observed in a highly ordered position 6 Å (1 Å=0.1 nm) removed from that seen in the Na+-bound state. The movement of the Na+ loop results in non-catalytic hydrogen-bonding in the active site and blocking of the S1 and S2 substrate-binding pockets. Similar, if more dramatic, changes were observed in a previous structure of the constitutively slow thrombin variant E217K. The slow behaviour of thrombin in solutions devoid of Na+ can now be understood in terms of an equilibrium between an inert species, represented by the crystal structure described in the present paper, and an active form, where the addition of Na+ populates the active state.
The family feud: turning off Sp1 by Sp1-like KLF proteins
Authors: Lomberk Gwen , Urrutia Raul
Published: November 2005

Sp1 is one of the best characterized transcriptional activators. The biological importance of Sp1 is underscored by the fact that several hundreds of genes are thought to be regulated by this protein. However, during the last 5 years, a more extended family of Sp1-like transcription factors has been identified and characterized by the presence of a conserved DNA-binding domain comprising three Krüppel-like zinc fingers. Each distinct family member differs in its ability to regulate transcription, and, as a consequence, to influence cellular processes. Specific activation and repression domains located within the N-terminal regions of these proteins are responsible for these differences by facilitating interactions with various co-activators and co-repressors. The present review primarily focuses on discussing the structural, biochemical and biological functions of the repressor members of this family of transcription factors. The existence of these transcriptional repressors provides a tightly regulated mechanism for silencing a large number of genes that are already known to be activated by Sp1.
Phase and interfacial behavior of partially miscible symmetric Lennard-Jones binary mixtures
Authors: Diaz-Herrera Enrique , Ramirez-Santiago Guillermo , Moreno-Razo Jose A.
Published: November 2005

We have carried out extensive equilibrium molecular-dynamics simulations to study quantitatively the topology of the temperature versus density phase diagrams and related interfacial phenomena in a partially miscible symmetric Lennard-Jones binary mixture. The topological features are studied as a function of miscibility parameter, α=ϵAB∕ϵAA. Here ϵAA=ϵBB and ϵAB stand for the parameters related to the attractive part of the intermolecular interactions for similar and dissimilar particles, respectively. When the miscibility varies in the range 0<α<1, a continuous critical line of consolute points Tcons(ρ)—critical demixing transition line—appears. This line intersects the liquid-vapor coexistence curve at different positions depending on the values of α, yielding mainly three different topologies for the phase diagrams. These results are in qualitative agreement to those found previously for square-well and hard-core Yukawa binary mixtures. The main contributions of the present paper are (i) a quantitative analysis of the phase behavior and (ii) a detailed study of the liquid-liquid interfacial and liquid-vapor surface tensions, as function of temperature and miscibility as well as its relationship to the topological features of the phase diagrams.
Collision as a way of forming bimetallic nanoclusters of various structures and chemical compositions
Authors: Mariscal Marcelo M. , Dassie Sergio A. , Leiva Ezequiel P. M.
Published: November 2005

In the present work, a new way to obtain bimetallic nanoclusters of different structures and chemical compositions is proposed, which is based on computer simulations. Collision processes between two metal clusters of different natures are simulated through molecular-dynamics simulations using many-body potentials. Diverse diffusion mechanisms and structures can be observed, depending on the metals combined and the initial kinetic energies. The nanostructures we have found are core-shell (Pt–Au), alloyed (Pd–Au), and three-shell onionlike (Cu–Ag).
Transport properties of normal liquid helium: Comparison of various methodologies
Authors: Rabani Eran , Krilov Goran , Reichman David R. , Berne B. J.
Published: November 2005

We revisit the problem of self-diffusion in normal liquid helium above the λ transition. Several different methods are applied to compute the velocity autocorrelation function. Since it is still impossible to determine the exact result for the velocity autocorrelation function from simulation, we appeal to the computation of short-time moments to determine the accuracy of the different approaches at short times. The main conclusion reached from our study is that both the quantum mode-coupling theory and the numerical analytic continuation approach must be regarded as a viable and competitive methods for the computation of dynamical properties of quantum systems.
Global thermodynamics of hydrophobic cavitation, dewetting, and hydration
Authors: Ben-Amotz Dor
Published: November 2005

Pure water experimental and simulation results are combined to predict the thermodynamics of cavity formation, spanning atomic to macroscopic length scales, over the entire ambient liquid temperature range. The resulting cavity equation of state is used to quantify dewetting excess contributions to cavity formation thermodynamics and construct a thermodynamic perturbation theory of hydrophobic hydration. Predictions are compared with large cavity simulations and experimental rare-gas hydration thermodynamics data (for He, Ne, Ar, Kr, Xe, and Rn). Key findings include the strong temperature dependence of the critical length scale for hydrophobic dewetting and the evaluation of fundamental solute-solvent interaction contributions to rare-gas hydration chemical potentials.
Silicon carbide photoconductive switch for high-power, linear-mode operations through sub-band-gap triggering
Authors: Kelkar K. S. , Islam N. E. , Fessler C. M. , Nunnally W. C.
Published: November 2005

The analysis of a 6H silicon carbide (SiC) photoconductive switch, designed and packaged for high-power, linear-mode operations, is presented. The switch, fabricated from semi-insulating compensated SiC, is triggered by an optical source with photon energy less than the band-gap energy. Simulation models incorporating the effects of vanadium trap and nitrogen dopant in the compensation material show I-V characteristics that agree with measured values. The photoconductive switch has improved rise-time characteristics as compared to a gallium arsenide (GaAs) switch. The analysis also shows that improved performance at high power is possible through passivation using high-permittivity dielectric near the contact-semiconductor interface and by placing a p+ layer next to the cathode.
Fatigue-induced evolution of domain structure in ferroelectric lead zirconate titanate ceramics investigated by piezoresponse force microscopy
Authors: Shvartsman V. V. , Kholkin A. L. , Verdier C. , Lupascu D. C.
Published: November 2005

The evolution of the domain structure in lead zirconate titanate ceramics in the course of polarization fatigue is investigated by piezoresponse force microscopy. It is found that fatigue results in a strong modification of the domain structure. The domain patterns initially consisting of mainly 180° domains split into fine ferroelastic domains to relieve the mechanical stresses arising due to the continuous polarization switching. The observed distorted domain walls (or “wavy” domain patterns) are attributed to clamping by defect agglomerates. The biggest concentration of clamped domains is found in grains close to the electrode interface signifying that these are most damaged by fatigue. Furthermore, a preferred polarization orientation is observed near the electrodes. Postannealing of fatigued samples promotes the partial recovery of the initial domain structure. The results indicate the importance of nearby electrode grains in the polarization switching in polycrystalline materials.