bluuebunny/crossref_metadata_2025 huggingface dataset:
Localized Stabilization of Microtubules by Integrin- and FAK-Facilitated Rho Signaling
Authors: Palazzo Alexander F. , Eng Christina H. , Schlaepfer David D. , Marcantonio Eugene E. , Gundersen Gregg G.
Published: February 2004

Microtubule (MT) stabilization is regulated by the small guanosine triphosphate (GTP)–binding protein Rho and its effector, mammalian homolog of Diaphanous (mDia), in migrating cells, but factors responsible for localized stabilization at the leading edge are unknown. We report that integrin-mediated activation of focal adhesion kinase (FAK) at the leading edge is required for MT stabilization by the Rho-mDia signaling pathway in mouse fibroblasts. MT stabilization also involved FAK-regulated localization of a lipid raft marker, ganglioside G
M1
, to the leading edge. The integrin-FAK signaling pathway may facilitate Rho-mDia signaling through G
M1
, or through a specialized membrane domain containing G
M1
, to stabilize MTs in the leading edge of migrating cells.
Profiling the Thermoelectric Power of Semiconductor Junctions with Nanometer Resolution
Authors: Lyeo Ho-Ki , Khajetoorians A. A. , Shi Li , Pipe Kevin P. , Ram Rajeev J. , Shakouri Ali , Shih C. K.
Published: February 2004

We have probed the local thermoelectric power of semiconductor nanostructures with the use of ultrahigh-vacuum scanning thermoelectric microscopy. When applied to a
p-n
junction, this method reveals that the thermoelectric power changes its sign abruptly within 2 nanometers across the junction. Because thermoelectric power correlates with electronic structure, we can profile with nanometer spatial resolution the thermoelectric power, band structures, and carrier concentrations of semiconductor junctions that constitute the building blocks of thermoelectric, electronic, and optoelectronic devices.
Evolutionary Dynamics of Biological Games
Authors: Nowak Martin A. , Sigmund Karl
Published: February 2004

Darwinian dynamics based on mutation and selection form the core of mathematical models for adaptation and coevolution of biological populations. The evolutionary outcome is often not a fitness-maximizing equilibrium but can include oscillations and chaos. For studying frequency-dependent selection, game-theoretic arguments are more appropriate than optimization algorithms. Replicator and adaptive dynamics describe short- and long-term evolution in phenotype space and have found applications ranging from animal behavior and ecology to speciation, macroevolution, and human language. Evolutionary game theory is an essential component of a mathematical and computational approach to biology.
Inferring Cellular Networks Using Probabilistic Graphical Models
Authors: Friedman Nir
Published: February 2004

High-throughput genome-wide molecular assays, which probe cellular networks from different perspectives, have become central to molecular biology. Probabilistic graphical models are useful for extracting meaningful biological insights from the resulting data sets. These models provide a concise representation of complex cellular networks by composing simpler submodels. Procedures based on well-understood principles for inferring such models from data facilitate a model-based methodology for analysis and discovery. This methodology and its capabilities are illustrated by several recent applications to gene expression data.
Clustering Concepts
Authors: Simboli Brian , Zhang Min
Published: February 2004

RefViz 1.0
. Thomson ISI ResearchSoft, Berkeley, CA, 2003. $299.95.
www.refviz.com
.

This text analysis software allows researchers and students to visualize and explore thematic and conceptual connections among references from scientific literature.
Introductory Science and Mathematics Education for 21st-Century Biologists
Authors: Bialek William , Botstein David
Published: February 2004

Galileo wrote that “the book of nature is written in the language of mathematics”; his quantitative approach to understanding the natural world arguably marks the beginning of modern science. Nearly 400 years later, the fragmented teaching of science in our universities still leaves biology outside the quantitative and mathematical culture that has come to define the physical sciences and engineering. This strikes us as particularly inopportune at a time when opportunities for quantitative thinking about biological systems are exploding. We propose that a way out of this dilemma is a unified introductory science curriculum that fully incorporates mathematics and quantitative thinking.
EXOTIC MESONS FROM QUANTUM CHROMODYNAMICS WITH IMPROVED GLUON AND QUARK ACTIONS ON THE ANISOTROPIC LATTICE
Authors: MEI ZHONG-HAO , LUO XIANG-QIAN
Published: February 2004

Hybrid (exotic) mesons, which are important predictions of quantum chromodynamics (QCD), are states of quarks and antiquarks bound by excited gluons. First principle lattice study of such states would help us understand the role of "dynamical" color in low energy QCD and provide valuable information for experimental search for these new particles. In this paper, we apply both improved gluon and quark actions to the hybrid mesons, which might be much more efficient than the previous works in reducing lattice spacing error and finite volume effect. Quenched simulations were done at β=2.6 and on a ξ=3 anisotropic 123×36 lattice using our PC cluster. We obtain 2013±26±71 MeV for the mass of the 1-+ hybrid meson [Formula: see text] in the light quark sector, and 4369±37±99 MeV in the charm quark sector; the mass splitting between the 1-+ hybrid meson [Formula: see text] in the charm quark sector and the spin averaged S-wave charmonium mass is estimated to be 1302±37±99 MeV. As a byproduct, we obtain 1438±32±57 MeV for the mass of a P-wave 1++[Formula: see text] or [Formula: see text] meson and 1499±28±65 MeV for the mass of a P-wave 1++[Formula: see text] meson, which are comparable to their experimental value 1426 MeV for the f1(1420) meson. The first error is statistical, and the second one is systematical. The mixing of the hybrid meson with a four quark state is also discussed.
STELLAR COLLAPSE
Authors: FRYER CHRIS L.
Published: February 2004

The collapse of massive stars have been used to explain many of the largest outbursts known to mankind, from supernovae to hypernovae to gamma-ray bursts. These explosions differ in their level of asymmetry and the spectral energy of the photons they emit. It is likely that such a wide range in the nature of these explosions requires more than one explosion mechanism to extract the gravitational potential energy released during the collapse. Three major classes of mechanisms have been proposed: neutrino-driven, magnetic-field driven, collapsar (black hole accretion disk) driven. This review discusses each mechanism in turn, discussing the current state-of-the-art calculations along with their observational predictions. We conclude with a summary of the current observational constraints on these models.
Exercise attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in coronary arteries from adult female pigs
Authors: Woodman Christopher R. , Turk James R. , Rush James W. E. , Laughlin M. Harold
Published: February 2004

We tested the hypothesis that exercise training (Ex) attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in left anterior descending coronary arteries. Adult female pigs were fed a normal-fat (NF) or high-fat (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were trained or remained sedentary (Sed) for 16 wk, yielding four groups of pigs: 1) NF-Sed, 2) NF-Ex, 3) HF-Sed, and 4) HF-Ex. Sensitivity (EC50) to bradykinin (BK) was impaired in HF-Sed arteries. Ex improved BK-induced relaxation such that the EC50 and maximal response to BK in HF-Ex arteries was not different from that in NF-Sed and NF-Ex. ACh-induced constriction was less in HF-Ex arteries than in HF-Sed, NF-Sed, and NF-Ex. To determine the mechanism(s) by which HF and Ex affected responses to BK and ACh, vasoactive responses were assessed in the presence of NG-nitro-l-arginine methyl ester [l-NAME; to inhibit nitric oxide (NO) synthase], indomethacin (Indo; to inhibit cyclooxygenase), and l-NAME + Indo. l-NAME inhibited BK-induced relaxation in NF (not HF) arteries. Indo did not significantly alter relaxation to BK in NF arteries; however, relaxation was enhanced in HF-Sed arteries. Double blockade with l-NAME + Indo attenuated BK-induced relaxation in NF arteries and eliminated relaxation in HF arteries. Neither l-NAME nor Indo altered constrictor responses to ACh in NF or HF arteries; however, double blockade with l-NAME + Indo attenuated constriction to ACh in NF-Ex arteries. Endothelium-independent relaxation to sodium nitroprusside was enhanced in HF-Sed and HF-Ex arteries. Collectively, these results indicate that HF impaired endothelial function in coronary arteries by impairing production of NO and by enhancing production of a constrictor that was inhibited by Indo. Ex attenuated the effects of hypercholesterolemia by improving NO-mediated, endothelium-dependent relaxation and by reducing the influence of the Indo-sensitive constrictor.
Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity
Authors: Peng Ying-Jie , Prabhakar Nanduri R.
Published: February 2004

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250–300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15sof5%O2 + 5 min of 21% O2, 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of [Formula: see text] radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and [Formula: see text] radicals play an important role in SDIH-induced sensitization of the carotid body.
Effects of 18 days of bed rest on leg and arm venous properties
Authors: Bleeker M. W. P. , De Groot P. C. E. , Pawelczyk J. A. , Hopman M. T. E. , Levine B. D.
Published: February 2004

Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6° head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 ± 0.007 ml·100 ml-1·mmHg-1, post: 0.033 ± 0.007 ml·100 ml-1·mmHg-1; P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 ± 1.08 mmHg·ml-1·100 ml·min, post: 3.10 ± 1.00 mmHg·ml-1·100 ml·min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure·time), decreased in all subjects after bed rest (pre: 932 mmHg·min, post: 747 mmHg·min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.
Unusual Crystallization Behavior of Selenium in the Presence of Organic Molecules at Room Temperature
Authors: Ohtani Tsukio , Takayama Norihiro , Ikeda Kazuaki , Araki Masako
Published: February 2004

Amorphous Se was converted into fibrous crystals of hexagonal Se or polyhedral crystals of α-monoclinic Se when exposed to organic fluids at room temperature for several days. The growth phase was dependent upon the dielectric constant of the organic liquids. It is notable that hexagonal Se and α-monoclinic Se formed under vapors of d- and l-camphor, respectively. It is proposed that the organic compounds do not act as solvents, but play a catalytic role in the reactions.
Chiral analysis of butaclamol enantiomers in human plasma by HPLC using a macrocyclic antibiotic (vancomycin) chiral stationary phase and solid phase extraction
Authors: Aboul‐Enein Hassan Y. , Hefnawy Mohamed M.
Published: February 2004

An enantioseparation of the antipsychotic drug butaclamol in human plasma by high‐performance liquid chromatography (HPLC) with solid phase extraction is presented. The separation was achieved on the vancomycin macrocyclic antibiotic chiral stationary phase (CSP) Chirobiotic V with a polar ionic mobile phase (PIM) consisting of methanol : glacial acetic acid : triethylamine (100:0.2:0.05, v/v/v) at a flow rate of 0.5 ml/min. The detection wavelength was 262 nm. Bond Elut C18 solid phase extraction cartridges were used in the sample preparation of butaclamol samples from plasma. The method was validated over the range of 100–3,000 ng/ml for each enantiomer concentration (R2 > 0.999). Recoveries for (+)‐ and (−)‐butaclamol were in the range of 94–104% at the 300–2,500 ng/ml level. The method proved to be precise (within‐run precision ranged from 1.1–2.6% and between‐run precision ranged from 1.9–3.2%) and accurate (within‐run accuracies ranged from 1.5–5.8% and between‐run accuracies ranged from 2.7–7.7%). The limit of quantitation (LOQ) and limit of detection (LOD) for each enantiomer in human plasma were 100 ng/ml and 50 ng/ml, respectively. Chirality 16:147–152, 2004. © 2004 Wiley‐Liss, Inc.
Enantiomeric separation of dansyl amino acids using macrocyclic antibiotics as chiral mobile phase additives by narrow‐bore high‐performance liquid chromatography
Authors: Sharp V. Scott , Letts Maureen N. , Risley Donald S. , Rose John P.
Published: February 2004

Seven macrocyclic antibiotics were evaluated as chiral selectors for the enantiomeric separation of 11 dansyl amino acids using narrow‐bore high‐performance liquid chromatography (HPLC). The macrocyclic antibiotics were incorporated as mobile phase additives to determine the enantioselective effects on the chiral analytes. The resolution and capacity factor (k′) of each analyte were assessed while varying the structure of macrocyclic antibiotic and the mobile phase buffer pH. The selectivity of the chiral selectors was measured as a function of changes in these parameters. All 11 dansyl amino acids were separated by at least one of the chiral selectors. Three‐dimensional computer modeling of the more effective chiral selectors illustrated the importance of macrocyclic antibiotic structure concerning stereospecific analyte interaction. Chirality 16:153–161, 2004. © 2004 Wiley‐Liss, Inc.
Absorption, fluorescence, and cd spectroscopic study of chiral recognition by a binaphthyl‐derived chromogenic calixcrown host
Authors: Kubinyi Miklós , Pál Krisztina , Baranyai Péter , Grofcsik András , Bitter István , Grün Alajos
Published: February 2004

The (R)‐ and (S)‐enantiomers of a binaphthyl‐appended calix4crown‐6 ether with two 2,4‐dinitrophenylazo chromophore units ((R)‐1 and (S)‐1) as chiral hosts were tested in their reactions with the enantiomers of α‐methylbenzylamine ((R)‐MBA, (S)‐MBA)) and phenylglycinol ((R)‐PGL, (S)‐PGL) as chiral guests. The visible absorption spectra indicate a two‐step process: the first is a nonenantioselective proton transfer from the host to the guest, which is followed by the enantioselective real complexation. In the visible range of the CD spectra a positive/negative band belongs to the absorption of pure (R)‐1/(S)‐1, and a negative/positive exciton couplet to the absorption of (R)‐1‐(S)‐MBA/(S)‐1‐(R)‐MBA complexes. The latter phenomenon suggests that the complexation of amines is accompanied by a chiral arrangement of the two chromophore units in the hosts. The UV fluorescence of (R)‐1/(S)‐1 arising from the binaphthyl moiety is quenched by K+ ions, but not by the amine guests, showing that the interaction between the binaphthyl group and the complexed amines is weak. Chirality 16:174–179, 2004. © 2004 Wiley‐Liss, Inc.
Differential recognition of resveratrol isomers by the human estrogen receptor‐α: Molecular dynamics evidence for stereoselective ligand binding
Authors: Abou‐Zeid Laila A. , El‐Mowafy Abdalla M.
Published: February 2004

Resveratrol (RSVL) is a phytoestrogen that occurs naturally in two forms (trans‐ (E) and cis‐ (Z)). We have conducted molecular dynamics (MD) studies to differentially characterize the estrogen receptor‐α (ER‐α) binding profiles of RSVL stereoisomers. Favorable orientations for RSVL isomers at the ER‐α pocket were first inferred from (1) alignment with pharmacophoric elements of the pure ER‐α agonists estradiol (E2) and (2) assessment of ligand recognition by the ER‐α binding domain. Subsequently, these orientations for RSVL isomers were subjected to MD analyses versus E2. A 100‐picosecond MD simulation revealed that E2 contributed four stable hydrogen bonds with the key ER‐α pocket reasidue: Arg394, Glu353, His524, and Leu525. Further, E2 displayed favorable binding energy, conformational energy change (ΔE), and movement of the binding pocket residues (RMSd). Compared to E2, (E)‐RSVL lacked a hydrogen bond (HB) with His524 but formed three additional bonds with Gly521, Phe404, and Met343 of the ER‐α pocket. Further, (E)‐RSVL conferred more favorable energy of interaction, less favorable ΔE, but comparable RMSd values. In contrast, (Z)‐RSVL orientations missed hydrogen bonding (HB) with His524 and Leu525, two essential ligand binding residues, and/or produced considerably less favorable‐binding energy, −ΔE, and ‐RMSd values than did (E)‐RSVL. In conclusion, the present study demonstrates the utility of this MD model in distinguishing between RSVL stereoisomers. The weak binding of (Z)‐RSVL by the human ER‐α binding is congruent with its inferior ligand profiles in ER‐endowed biological systems. Further, evidence is provided for a considerable variation in the mode of recognition of the mixed agonist/antagonist (E)‐RSVL, and the pure agonist E2. Chirality 16:190–195, 2004. © 2004 Wiley‐Liss, Inc.
Enantioselective chromatography and molecular modeling of novel aryloxyaminopropan‐2‐ols with the alkyl carbamate function
Authors: Navrátilová Hana , Opatřilová Radka , Kříž Zdeněk , Koča Jaroslav
Published: February 2004

A series of different racemic aryloxyaminopropan‐2‐ol derivatives 1a‐d–3a‐d with potential β‐adrenergic blocking effects related to propanolol 4 and atenolol 5 was resolved by HPLC using Chiralcel OD‐H and Chiralpak AD as chiral stationary phases. Mobile phases consisted of a hexane/alcohol (propan‐2‐ol or ethanol) mixture doped with a modifier (DEA or TFA). The retention behavior of the compounds depended on the position of the carbamate attached to the aryloxy moiety and on the length of the alkyl residue in the carbamate. Enantiomers of the title compounds were baseline separated with the separation factors α and resolutions Rs varying in the range of 1.34–4.55 and 1.50–10.65, respectively. The chromatographic systems developed can be used for the determination of the enantiomeric purity of the title compounds. Molecular modelling using empirical molecular mechanics and ab initio quantum chemistry methods provided low‐energy structures in which sites of potential interactions responsible for retention behavior and chiral recognition could be identified. Chirality 16:139–146, 2004. © 2004 Wiley‐Liss, Inc.
A randomized controlled trial of darbepoetin alfa administered as a fixed or weight‐based dose using a front‐loading schedule in patients with anemia who have nonmyeloid malignancies
Authors: Hesketh Paul J. , Arena Francis , Patel Dhimant , Austin Matt , D'Avirro Paul , Rossi Gregory , Colowick Alan , Schwartzberg Lee
Published: February 2004

BACKGROUND

The effect of using fixed versus weight‐based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight‐based dose using an accelerated correction and maintenance dosing regimen (front‐loading).

METHODS

During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325μg (n = 122) or at a weight‐based dose of 4.5 μg/kg (n = 120) once weekly until they achieved a hemoglobin concentration ≥ 12.0 g/dL. Patients then received darbepoetin alfa (325 μg or 4.5 μg/kg) once every 3 weeks for the remainder of the 16‐week treatment period (maintenance phase).

RESULTS

Darbepoetin alfa resulted in high Kaplan–Meier rates of hematopoietic response (≥ 2 g/dL increase from the baseline level or a hemoglobin level ≥ 12 g/dL) in both the fixed‐dose group (86%; 95% confidence interval [95% CI], 78– 94%) and the weight‐based dose group (84%; 95% CI, 76–92%). The median time to hematopoietic response was 34 days (95% CI, 28–44 days) for the fixed‐dose group and 36 days (95% CI, 30–45 days) for the weight‐based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight‐based doses were observed.

CONCLUSIONS

Darbepoetin alfa was effective when administered as either a fixed dose or a weight‐based dose using a front‐loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease. Cancer 2004;100:859–68. © 2004 American Cancer Society.
Adjuvant therapy of osteosarcoma—A Phase II trial
Authors: Zalupski Mark M. , Rankin Cathryn , Ryan James R. , Lucas David R. , Muler Jeffrey , Lanier Keith S. , Budd George Thomas , Biermann J. Sybil , Meyers Frederick J. , Antman Karen
Published: February 2004

BACKGROUND

The objective of this study was to estimate the time to treatment failure and survival rate of the three‐drug combination of doxorubicin, cisplatin, and ifosfamide as primary and postoperative, adjunctive treatment for teenagers and adults with osteosarcoma (OS).

METHODS

Sixty‐three eligible patients with nonmetastatic OS of the extremities were registered from 24 institutions from February, 1992 through December, 1996. Chemotherapy was comprised of doxorubicin at a dose of 75 mg/m2 and cisplatin at a dose of 120 mg/m2, alternating with doxorubicin at a dose of 50 mg/m2 and ifosfamide at a dose of 8 g/m2. Four cycles were given prior to surgical resection, and four cycles were given after surgery. Outcome measures included the time to treatment failure, overall survival, toxicity, and centralized assessment of tumor necrosis.

RESULTS

Thirty‐one of 63 eligible patients died, for a 5‐year overall survival rate of 58% (95% confidence interval [95% CI], 46–71%). The median time to treatment failure was 19 months (95% CI, 12–41 months). A good pathologic response (≥ 90% necrosis) to neoadjuvant chemotherapy was observed in 48% of patients who underwent surgery. There was no correlation noted between response to neoadjuvant chemotherapy and patient outcome. Grade 4 hematologic toxicities were frequent (89%), although serious nonhematologic toxicities other than nausea and emesis were uncommon.

CONCLUSIONS

The regimen and schedule used in the current study did not improve outcomes compared with prior trials of doxorubicin and cisplatin alone. New, more effective drugs are needed for the treatment of patients with OS. The identification and utilization of molecular markers to predict outcome and response to therapy would facilitate clinical management, limiting exposure to toxic therapies for patients with favorable molecular profiles and identifying those patients who may fail with current approaches as candidates for clinical trials. Cancer 2004;100:818–25. © 2004 American Cancer Society.
Quality of life and pain relief during treatment with calcitriol and docetaxel in symptomatic metastatic androgen‐independent prostate carcinoma
Authors: Beer Tomasz M. , Eilers Kristine M. , Garzotto Mark , Hsieh Yi‐Ching , Mori Motomi
Published: February 2004

BACKGROUND

The current study evaluated the analgesic activity and impact on quality of life (QOL) of a new chemotherapy regimen of calcitriol and docetaxel in men with androgen‐independent prostate carcinoma.

METHODS

Analgesic response was defined as a 2‐point reduction on the Present Pain Intensity (PPI) scale (or compete relief if baseline PPI was 1) without an increase in analgesic use or a 50% decrease in analgesic medication use without an increase in pain, maintained for ≥ 4 weeks. Pain, pain medication consumption, and QOL (measured by the European Organization for Research and Treatment of Cancer QLQ‐C30) were evaluated every 4 weeks.

RESULTS

Treatment resulted in an analgesic response in 14 of 29 evaluable patients (48%; 95% confidence interval [95% CI], 30–67%). The median time to symptomatic progression in the 14 patients who met criteria for analgesic response was 41 weeks (95% CI, 26–56 weeks). Worsening in physical and role functioning, fatigue, appetite, and global health status and improvement in constipation were detected using the QLQ‐C30 QOL questionnaire.

CONCLUSIONS

Significant analgesic activity was demonstrated, although worsening in several QOL domains was observed in a patient population with relatively low pain intensity (median PPI, 2). Cancer 2004;100:758–63. © 2004 American Cancer Society.
The natural history of incidentally detected small renal masses
Authors: Volpe Alessandro , Panzarella Tony , Rendon Ricardo A. , Haider Masoom A. , Kondylis Filippos I. , Jewett Michael A. S.
Published: February 2004

BACKGROUND

The incidence of renal cell carcinoma (RCC) is increasing, largely due to the widespread use of cross‐sectional imaging. Most renal tumors are detected incidentally as small, asymptomatic masses. To study their natural history, the authors prospectively followed a series of patients with this type of lesion who were unsuited for or refused surgery.

METHODS

Twenty‐nine patients with 32 masses that measured < 4 cm in greatest dimension (25 solid masses and 7 complex cystic masses) were studied. The primary outcome was tumor size, which was calculated as volume over time. All patients were followed with serial abdominal imaging, and each mass had at least three follow‐up measurements. The median follow‐up was 27.9 months (range, 5.3–143.0 months).

RESULTS

Overall, the average growth rate did not differ statistically from zero growth (P = 0.09; 95% confidence interval, − 0.005–0.2 cm per year) and was not associated with either initial size (P = 0.28) or mass type (P = 0.41). Seven masses (22%) reached 4 cm in greatest dimension after 12–85 months of follow‐up. Eight masses (25%) doubled their volumes within 12 months. Overall, 11 masses (34%) fulfilled 1 of these 2 criteria of rapid growth. Nine tumors were removed surgically after an average of 3.1 years of follow‐up because it was believed that they were growing fast. No patient had disease progression.

CONCLUSIONS

Approximately one‐third of small renal masses that are presumed RCCs grow if they are managed conservatively and are followed with serial imaging. The growth rate is slow or undetectable in the majority of patients. These observations raise the possibility of a period of initial observation in selected patients, particularly the elderly or infirm. Cancer 2004;100:738–45. © 2004 American Cancer Society.
Mammalian target of rapamycin inhibition as therapy for hematologic malignancies
Authors: Panwalkar Amit , Verstovsek Srdan , Giles Francis J.
Published: February 2004

The mammalian target of rapamycin (mTOR) is a downstream effector of the phosphatidylinositol 3‐kinase (PI3K)/Akt (protein kinase B) signaling pathway, which mediates cell survival and proliferation. mTOR regulates essential signal‐transduction pathways, is involved in the coupling of growth stimuli with cell cycle progression, and initiates mRNA translation in response to favorable nutrient environments. mTOR is involved in regulating many aspects of cell growth, including membrane traffic, protein degradation, protein kinase C signaling, ribosome biogenesis, and transcription. Because mTOR activates both the 40S ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 4E‐binding protein 1, its inhibitors cause G1‐phase cell cycle arrest. Inhibitors of mTOR also prevent cyclin dependent kinase (CDK) activation, inhibit retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help cause G1‐phase arrest. It is known that the phosphatase and tensin homologue tumor suppressor gene (PTEN) plays a major role in embryonic development, cell migration, and apoptosis. Malignancies with PTEN mutations, which are associated with constitutive activation of the PI3K/Akt pathway, are relatively resistant to apoptosis and may be particularly sensitive to mTOR inhibitors. Rapamycin analogs with relatively favorable pharmaceutical properties, including CCI‐779, RAD001, and AP23573, are under investigation in patients with hematologic malignancies. Cancer 2004;100:657–66. © 2004 American Cancer Society.
Clinical significance of bone marrow microinvolvement in nonsmall cell lung carcinoma
Authors: Hsu Chung‐Ping , Shai Sen‐Ei , Hsia Jiun‐Yi , Chen Chih‐Yi
Published: February 2004

BACKGROUND

The divergences in the clinical significance of bone marrow microinvolvement (BMM) in patients with nonsmall cell lung carcinoma (NSCLC) necessitated a long‐term large series study.

METHODS

Between March 1997 and June 2001, the authors analyzed 212 bone marrow specimens (from the posterior iliac crest) taken from patients with NSCLC before surgery. The degree of tumor differentiation included well differentiated carcinoma in 12 Patients, moderately differentiated carcinoma in 112 Patients, and poorly differentiated carcinoma in 68 Patients. The pTNM staging (according the the criteria of the American Joint Committee on Cancer) included Stage IA in 8 patients, Stage IB in 70 patients, Stage IIB in 36 patients, Stage IIIA in 54 patients, Stage IIIB in 14 patients, and Stage IV in 10 patients. The specimens were evaluated by immunohistochemical staining with antihuman cytokeratin AE1/AE3, Ber‐EP4, and clone MNF116 mixed solution to detect the presence of malignant epithelial cells in the bone marrow.

RESULTS

Positive results were observed in 66 patients (34.4%). The occurrence of BMM was not found to be related to patient age, gender, cell type, or TNM status. The 5‐year disease‐free survival rates were 44.9% and 40.5% in BMM‐negative and BMM‐positive patients, respectively (P = 0.3797). The 5‐year cumulative survival rates were 43.5% and 44.0% in BMM‐negative and BMM‐positive patients, respectively (P = 0.4262). Multivariate analysis failed to demonstrate BMM as an independent prognostic factor (P = 0.1817).

CONCLUSIONS

The results of the current study showed that although BMM was observed frequently in patients with NSCLC, regardless of tumor stage and pathologic types, its occurrence was not a good predictor of long‐term prognosis. Cancer 2004;100:794–800. © 2004 American Cancer Society.
Therapeutic efficacy of once‐daily oral administration of a Kunitz‐type protease inhibitor, bikunin, in a mouse model and in human cancer
Authors: Kobayashi Hiroshi , Yagyu Tatsuo , Inagaki Kiyokazu , Kondo Toshiharu , Suzuki Mika , Kanayama Naohiro , Terao Toshihiko
Published: February 2004

BACKGROUND

Bikunin, a Kunitz‐type protease inhibitor, specifically inhibits tumor invasion and metastasis.

METHODS

The authors initially evaluated the therapeutic efficacy of once‐daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7‐week‐old nude mice were randomized to 1 of 4 groups: bikunin‐treated groups (n = 9 in each group) received 3, 10, or 30 μg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate‐buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment.

RESULTS

After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once‐daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum‐tolerated dose (MTD) and safety of a once‐daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose‐limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase‐type plasminogen activator expression at the highest dose level.

CONCLUSIONS

Once‐daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Cancer 2004;100:869–77. © 2004 American Cancer Society.
Impact of hydroelectric power releases on the morphology and sedimentology of the bed of the Warche River (Belgium)
Authors: Assani A. A. , Petit F.
Published: February 2004

The Butgenbach dam on the Warche River was built in 1932 in order to maintain a sufﬁcient supply of water to the Robertville reservoir situated 7 km downstream, for the production of hydroelectricity. During winter months, releases are made almost every day from the Butgenbach dam. From a hydrological point of view, this has resulted in signiﬁcantly reducing the number of discharges that are higher than bankfull. Despite the reduction in peak discharge, there is a signiﬁcant increase in the number of efﬁcient discharges (0·6 bankfull). The impacts of these hydrological modiﬁcations on the bed morphology and sedimentology below the Butgenbach dam have been studied and the following geomorphological modiﬁcations have been identiﬁed: a doubling of the width of the channel in 45 years, a reduction in the number of rifﬂes and pools, an increase in the number of gravel bars and islets and an increase in bedrock outcrops in the channel. Moreover, the ﬁnest bed particles are mobilized by the almost daily releases, inducing a signiﬁcant increase in bed‐material size sorting. The reduction of sinuosity and the disappearance of bed differentiation and rifﬂe/pool sequences have produced a diminution of bed roughness and an increase of the competence of the river. Thus relatively small ﬂoods can remove the armoured layer. Copyright © 2003 John Wiley & Sons, Ltd.
Tilting neotectonics of the Guadiamar drainage basin, SW Spain
Authors: Salvany Josep M.
Published: February 2004

The Guadiamar river ﬂows from the southern Iberian Massif to the Guadalquivir foreland basin, SW Spain. Its drainage basin displays asymmetries in the stream network, the arrangement of alluvial terraces and the conﬁguration of the trunk river valley. The stream network asymmetry was studied using morphometric measures of transverse topographic sym‐metry, asymmetry factor and drainage basin shape. The alluvial terraces were studied through the lithologic logs of more than a hundred boreholes and ﬁeld mapping. The morphometric methods demonstrate a regional tectonic tilting toward the SSE, causing both the migration of the Guadiamar river toward the east and the migration of the Guadiamar tributaries toward the southwest. As a consequence of the Guadiamar river migration, an asymmetric valley developed, with a steep eastern margin caused by river dissection, and a gentle western margin where the main alluvial deposits are found. The ages obtained using the 14C analysis of samples from several alluvial deposits show that the river migration, and thus tilting, has occurred during the Holocene as well as earlier in the Quaternary. This interpretation revises the Guadiamar longitudinal fault assumed by previous studies. Copyright © 2003 John Wiley & Sons, Ltd.
Drainage basin sensitivity to tectonic and climatic forcing: implications of a stochastic model for the role of entrainment and erosion thresholds
Authors: Tucker Gregory E.
Published: February 2004

Long‐term average rates of channel erosion and sediment transport depend on the frequency–magnitude characteristics of ﬂood ﬂows that exceed an erosion threshold. Using a Poisson model for rainfall and runoff, analytical solutions are developed for average rates of stream incision and sediment transport in the presence of such a threshold. Solutions are derived and numerically tested for three erosion/transport formulas: the Howard–Kerby shear‐stress incision model, the Bridge–Dominic sediment transport model, and a generic shear‐stress sediment transport model. Results imply that non‐linearity resulting from threshold effects can have a ﬁrst‐order impact on topography and patterns of dynamic response to tectonic and climate forcing. This non‐linearity becomes signiﬁcant when fewer than about half of ﬂood events are capable of detaching rock or sediment. Predicted morphology and uplift‐gradient scaling is more closely consistent with observations and laboratory experiments than conventional slope‐linear or shear‐linear erosion laws. These results imply that particle detachment thresholds are not details that can be conveniently ignored in long‐term landscape evolution models. Copyright © 2004 John Wiley & Sons, Ltd.
Estimation of debris‐flow magnitude in the Eastern Italian Alps
Authors: Marchi Lorenzo , D'Agostino Vincenzo
Published: February 2004

The estimation of debris‐ﬂow magnitude is an essential step in the assessment of debris‐ﬂow hazard. Although different methods have been developed for the assessment of debris‐ﬂow magnitude, this is still a difﬁcult task because of the complexity of ﬂow processes and the lack of data to test estimation procedures in many mountainous regions. Data on debris‐ﬂow magnitude from 127 basins in the Eastern Italian Alps have been collected from scientiﬁc and technical journals, technical reports, historical documents gathered from local archives, and ﬁeld surveys. These data were used to develop and test different predictive approaches, encompassing regression equations, geomorphological surveys and probabilistic analysis of time series. Regression techniques were used to correlate debris‐ﬂow magnitude to morphometric parameters and geological characteristics of the basins. Values of the channel debris yield rate (contribution per unit length of channel), proposed in the literature, were compared with data from the study area for identifying reference values for channel stretches of different morphological characteristics. Although limited to the few basins in which sufﬁcient data were available, the probabilistic analysis of time series of debris‐ﬂow magnitude provides indications about the relations between magnitude and frequency of debris ﬂows. Some observations about the capability and drawbacks of considered methods are presented and the combined use of different approaches for the estimation of debris‐ﬂow magnitude is suggested. Copyright © 2004 John Wiley & Sons, Ltd.
Landslide incidence zonation in the Rio Mendoza valley, Mendoza Province, Argentina
Authors: Moreiras Stella M.
Published: February 2004

This paper presents a landslide incidence zonation map showing the percentage of underlying material involved in mass‐movement processes in the Rio Mendoza valley, Argentina. The landslide incidence zonation map was derived from an inventory map of landslides and reveals that many areas of the Rio Mendoza valley are implicated in this kind of process. A correlation has been found between the occurrence of landslides, earthquakes, and rainfall. The relation between lithology and landslides is clear: areas covered by friable sedimentary and volcanic rocks of the Choiyoi Group are prone to debris ﬂows and complex landslides. The slope map has been ranked and a general relation between slope and type of event is shown. Falls commonly develop in high‐angle slopes. Copyright © 2004 John Wiley & Sons, Ltd.
A homodyne five‐port network analyzer operating in the W‐frequency band
Authors: Chahine S. Abou , Huyart B.
Published: February 2004

This paper presents a homodyne five‐port network analyzer operating at 94 GHz using a single five‐port junction. The homodyne detection is realized using a PIN diode amplitude modulator and an AC detection technique. The obtained results show that the system can operate at very low power with no need for detector linearization. The proposed system as well as the exact equations in the two operating modes—reflection and transmission—are described. New calibration procedures, with and without matched loads, are proposed for the two operating modes. Practical measurements, in reflection as well as in transmission, prove the validity and the high efficiency of the system. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 444–448, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20001
Wave propagation in metamaterial multi‐layered structures
Authors: Cory H. , Zach C.
Published: February 2004

Expressions are given for the overall reflection and transmission coefficients of a multilayered structure consisting of metamaterial and dielectric slabs. Small‐reflection approximations are discussed. Two applications are proposed: anti‐reflection coatings and high‐reflection coatings. For the first application, a structure consisting of two slabs of the same width and opposite permittivities is studied. If the structure is placed between two semi‐infinite media of the same kind, the reflection vanish, while if these two media are different, the reflection depends only on their characteristics and on the angle of incidence. This device could be advantageously used as an antenna radome. For the second application, a structure consisting of a large number of identical pairs of slabs of high and low opposite permittivities and of the same widths, embedded in the same medium, is studied. This structure's transmittance variation with frequency shows no ripples, and has a large passband and a monotonous quasi‐symmetric rise to the right and to the left of the central frequency. The distinctive feature of these devices is the weakening of the influence of the frequency, the angle of incidence or the polarization on the propagation processes. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 460–465, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20005
Stepped impedance resonator bandpass filters using tapped‐line for controlling spurious response
Authors: Weng Min‐Hung , Chen Wu‐Nan , Huang Tsung‐Hui , Hung Cheng‐Yuan , Wu Hung‐Wei
Published: February 2004

A stepped impedance resonator bandpass filter was designed and implemented, combining with the tapped‐line structure. The measured bandpass filters at the center frequency of 2.0 GHz has the characteristics: the insertion lossS21= −2.98 dB, BWR is 15.1%, and the transmission zeros occurred at 2.62 GHz with −48.5 dB. Especially, the wider rejection of −20 dB can be obtained form 2.4 to 8.2 GHz from the proper position of tapped‐line I/O. The designed filter shows the excellent abilities to shift and suppress the spurious response by properly designing the structure of the resonator. The proposed filter was designed and fabricated, and the performances closely matched the simulation results. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 481–484, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20010
Finite‐element analysis of phased‐array antennas
Authors: Lou Zheng , Jin Jian‐Ming
Published: February 2004

The finite‐element method (FEM) is applied to the analysis of phased‐array antennas. Curvilinear tetrahedral elements are used for domain discretization and high‐order vector basis functions are used for field expansion. Periodic boundary and radiation conditions are enforced on a single unit cell in the infinite array. A waveguide port condition is also implemented to accurately model the field on the aperture of the coaxial line that provides excitation. The asymptotic waveform evaluation (AWE) technique is combined with the FEM to perform fast‐frequency and angular sweeps. The computed antenna parameters are compared with previously published results and good agreement is obtained. The effects of different feeding schemes on the array parameters are studied and compared. Frequency responses and scan performance of a flared‐notch antenna design are presented. Finally, a preliminary investigation is made on the validity of the infinite‐array approximation to the corresponding finite‐array problems. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 490–496, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20013
Magnetoplasmon dispersion on an n‐GaAs/dielectric interface at 77°K
Authors: Mok V. H. , Davis L. E.
Published: February 2004

Surface magnetoplasmons on a single semiconductor–dielectric interface in a transverse static magnetic flux have been modelled. The dispersion diagrams exhibit nonreciprocal behaviour for the forward and reverse propagation as expected, but the effect of the permittivity of the dielectric is shown for the first time. The elliptical polarization of the electric field in both media, near the interface, above and below the EWR frequency, for both directions of propagation is computed. The results have implications for the development of miniature isolators and phase shifters at millimetric and submillimetric wavelengths. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 505–509, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20017