bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic indicators in peritoneal carcinomatosis from gastrointestinal cancer
Authors: Harmon Rhonda L , Sugarbaker Paul H
Published: February 2005

Peritoneal carcinomatosis from gastrointestinal cancer has new treatment options for surgical management. The approach uses cytoreductive surgery which combines peritonectomy and visceral resection in an effort to remove all visible cancer within the abdomen and pelvis. Then the peritoneal cavity is flooded with chemotherapy solution in an attempt to eradicate residual disease. In order to select patients for this approach the quantitative prognostic indicators for carcinomatosis were reviewed, compared and contrasted. Prognostic indicators to be used to select patients for this aggressive approach at the initiation of surgery and after completion of cytoreduction were studied. Four quantitative assessments to be used at the time of abdominal exploration were the Gilly staging, Japanese gastric cancer P score, peritoneal cancer index (PCI), and the simplified peritoneal cancer index (SPCI). All have value with the PCI being the most validated and most precise. Preoperative assessments include the tumor histopathology and the prior surgical score. The completeness of cytoreduction score is an assessment of residual disease after a maximal surgical effort. An opportunity for long-term survival following treatment for carcinomatosis requires a complete cytoreduction in all reports for gastrointestinal cancer. Quantitative prognostic indicators need to be knowledgeably employed when patients with carcinomatosis are being treated. Improved patient selection with greater benefit and reduced morbidity and mortality should result.
Steering drift and wheel movement during braking: Static and dynamic measurements
Authors: Klaps J , Day A J
Published: February 2005

This paper reports on an experimental investigation into braking-related steering drift in motor vehicles, and follows on from a previous paper by the authors in which it was concluded that braking can cause changes in wheel alignment that in turn affect the toe-steer characteristics of each wheel and therefore the straight-line stability of the vehicle during braking. Changes in suspension geometry during braking, their magnitude and the relationships between the braking forces and the suspension geometry and compliance are further investigated in an experimental study of wheel movement arising from compliance in the front suspension and the steering system of a passenger car during braking. Using a kinematic and compliance (K&C) test rig, movement of the front wheels and the suspension subframe, together with corresponding changes in suspension and steering geometry under simulated braking conditions, have been measured and compared with dynamic measurements of the centre points of the front wheels. The results have enabled the causes and effects of steering drift during braking to be better understood in the design of front suspension systems for vehicle stability during braking.
Design of hydromechanical transmission using network analysis
Authors: Sung Dukhwan , Hwang Sungho , Kim Hyunsoo
Published: February 2005

A systematic approach to the design of a three-shaft hydromechanical transmission (HMT) is proposed. The three-shaft HMT is classified into 12 basic configurations depending on the planetary gear position connected with the hydrostatic unit (HSU) at the input and the output shafts. The power and speed characteristics are investigated for 12 configurations of the three-shaft HMT using network analysis. Based on the results of the network analysis of the three-shaft HMT, design examples are proposed in a systematic way, which limit the circulation power and allow synchronous clutch operation. It is expected that the design methodology suggested in this study can be used in developing the three-shaft HMT to meet power and speed requirements.
Wheel slip tracking using moving sliding surface
Authors: Chun Kyunghan , Sunwoo Myoungho
Published: February 2005

This paper describes robust and fast wheel slip control using a moving sliding surface technique. Unlike the conventional sliding mode control, the moving sliding surface moves (shifts and rotates) to the desired sliding surface from the initial condition and thus fast tracking can be obtained. In addition, the moving sliding mode was originally designed to ensure that the states remain on a sliding surface, thereby simultaneously achieving robustness and eliminating chattering at the same time. In vehicle dynamics, the wheel slip during driving can change because of environmental variations which always happen in driving conditions. The moving sliding surface technique is applied to wheel slip control to obtain a robust and fast response. The design strategy is based on a moving sliding surface that only contains the error between the reference input wheel slip and the actual wheel slip. The proposed controller can track a reference input wheel slip in a predetermined time. Simulations are performed and analysed to demonstrate the effectiveness of the proposed moving sliding-mode controller.
Improvement in fuel economy for a parallel hybrid electric vehicle by continuously variable transmission ratio control
Authors: Lee H , Kim H
Published: February 2005

A continuously variable transmission (CVT) ratio control algorithm is proposed to achieve the improved fuel economy of the parallel hybrid electric vehicle (HEV) by considering the HEV powertrain response lag. In this algorithm, the target CVT ratio is modified by the vehicle velocity that is estimated after the powertrain response lag. To estimate the vehicle velocity after the response lag, an acceleration map is suggested. The CVT ratio control algorithm is validated by the HEV bench tester. From experimental results, it is found that the engine operation trajectory by the modified ratio control algorithm is shifted to a more efficient region compared with those by the conventional CVT ratio control for the mild acceleration mode, which gives better fuel economy. In addition, performance simulations for the federal urban driving schedule are carried out to evaluate the effect of the response lag on the HEV fuel economy using the HEV powertrain model. The simulation results show that a better fuel economy can be achieved as the response lag used in the modified CVT ratio increases. However, in actual applications, a compromise between the fuel economy and the acceleration performance would be required.
Constraint-Propagation-Based Cutting Planes: An Application to the Resource-Constrained Project Scheduling Problem
Authors: Demassey Sophie , Artigues Christian , Michelon Philippe
Published: February 2005

We propose a cooperation method between constraint programming and integer programming to compute lower bounds for the resource-constrained project scheduling problem (RCPSP). The lower bounds are evaluated through linear-programming (LP) relaxations of two different integer linear formulations. Efficient resource-constraint propagation algorithms serve as a preprocessing technique for these relaxations. The originality of our approach is to use additionally some deductions performed by constraint propagation, and particularly by the shaving technique, to derive new cutting planes that strengthen the linear programs. Such new valid linear inequalities are given in this paper, as well as a computational analysis of our approach. Through this analysis, we also compare the two considered linear formulations for the RCPSP and confirm the efficiency of lower bounds computed in a destructive way.
Oblique Multicategory Decision Trees Using Nonlinear Programming
Authors: Street W. Nick
Published: February 2005

Induction of decision trees is a popular and effective method for solving classification problems in data-mining applications. This paper presents a new algorithm for multi-category decision tree induction based on nonlinear programming. This algorithm, termed OC-SEP (Oblique Category SEParation), combines the advantages of several other methods and shows improved generalization performance on a collection of real-world data sets.
Numerical Solutions of Renewal-Type Integral Equations
Authors: Tortorella Michael
Published: February 2005

The integral equation of renewal type has many applications in applied probability. However, it is rarely solvable in closed form. In this paper, we describe a numerical method for finding approximate solutions to integral equations of renewal type based on quadrature rules for Stieltjes integrals previously developed by the author. We provide error analyses for our numerical solution based on the trapezoid-like rule for Stieltjes integrals and describe computational experience with two solution algorithms based on the trapezoid-like and the Simpson-like rules for Stieltjes integrals. We discuss a link between discrete and continuous renewal theory that is illuminated by the numerical solution method. The proposed numerical method is simple, amenable to direct error analysis, performs better than previously proposed approximations in many cases of significant practical interest, and is capable of handling some cases on which other methods fail.
Evolving Role of Low-Molecular-Weight Heparins in ST-Elevation Myocardial Infarction
Authors: Kalus James S , Moser Lynette R
Published: February 2005

OBJECTIVE:

To review the available literature on the efficacy and safety of low-molecular-weight heparin (LMWH) in the treatment of ST-elevation myocardial infarction (STEMI) in patients treated with fibrinolytic therapy or conservative medical management.

DATA SOURCES:

A MEDLINE search (1966–March 2004) using the key words myocardial infarction, STEMI, LMWH, enoxaparin, and dalteparin identified pertinent articles. The references of these articles were reviewed for additional pertinent references.

STUDY SELECTION AND DATA EXTRACTION:

All human trials of LMWH in STEMI were evaluated. All pertinent studies were included in the review.

DATA SYNTHESIS:

LMWH did not show a benefit in STEMI without fibrinolytic therapy. Enoxaparin is similar to intravenous unfractionated heparin (UFH) in combination with nonspecific fibrinolytic therapy with regard to invasive reperfusion markers and 30-day clinical outcomes. Enoxaparin decreases composite endpoints in combination with fibrin-specific fibrinolytic therapy compared with UFH, primarily through a reduction in the incidence of reinfarction at 30 days. Bleeding rates with LMWH in combination with fibrinolytic agents are not greater than those with UFH.

CONCLUSIONS:

Enoxaparin is a reasonable alternative to UFH in patients with STEMI treated with fibrin-specific fibrinolytic therapy. LMWH in patients managed with nonspecific fibrinolytic therapy or conservative medical treatment does not provide an advantage over standard management. Large clinical trials are ongoing which will provide more definitive recommendations.
Infrequency of Sexually Transmitted Disease Screening Among Sexually Experienced U.S. Female Adolescents
Authors: Fiscus Lynne C. , Ford Carol A. , Miller William C.
Published: February 2005

CONTEXT: Since 1993, the Centers for Disease Control and Prevention and professional medical organizations have recommended that all sexually experienced female adolescents receive annual screening for Chlamydia trachomatis. Whether adolescents receive this care is largely unknown.

METHODS: Reports of receipt of testing or treatment for a sexually transmitted disease (STD) in the past year, as well as sites of care, were obtained from 3,987 sexually experienced females in grades 7–12 who participated in Wave 1 of the National Longitudinal Study of Adolescent Health, conducted in 1995. Logistic regression was used to determine predictors of reporting care.

RESULTS: Eighteen percent of all participants reported having received STD services in the past year. Of those who reported having had a routine physical examination in the past year, 22% reported receipt of STD services. The proportion reporting STD care increased linearly with age from 9% of 12–13‐year‐olds to 25% of those 19 or older. In adjusted analyses, the odds of reporting testing or treatment were elevated among participants who had had a physical examination in the past year (odds ratio, 2.1), those with Medicaid or Medicare insurance (1.9), black women (1.5) and older adolescents (1.2). Adolescents most often reported having received STD care at a community health center (44%) or a private physician's office (31%).

CONCLUSIONS: Continued inadequate screening may contribute to persisting high prevalence of chlamydia infection among adolescents. Future research is needed to determine whether the proportions of adolescents receiving recommended STD screening have increased over time.
Contraceptive Use and Consistency in U.S. Teenagers' Most Recent Sexual Relationships
Authors: Manlove Jennifer , Ryan Suzanne , Franzetta Kerry
Published: February 2005

CONTEXT: Most U.S. teenage pregnancies are unintended, partly because of inconsistent or no use of contraceptives. Understanding the factors associated with contraceptive use in teenagers' most recent relationships can help identify strategies to prevent unintended pregnancy.

METHODS: Data on 1,468 participants in Waves 1 and 2 of the National Longitudinal Study of Adolescent Health who had had two or more sexual relationships were analyzed to assess factors associated with contraceptive use patterns in teenagers' most recent sexual relationship. Odds ratios were generated through logistic regression.

RESULTS: Many relationship and partner characteristics were significant for females but nonsignificant for males. For example, females' odds of ever, rather than never, having used contraception in their most recent relationship increased with the duration of the relationship (odds ratio, 1.1); their odds were reduced if they had not known their partner before dating him (0.2). The odds of consistent use (vs. inconsistent or no use) were higher for females in a “liked” relationship than for those in a romantic relationship (2.6), and for females using a hormonal method instead of condoms (4.5). Females' odds of consistent use decreased if the relationship involved physical violence (0.5). Among teenagers in romantic or “liked” relationships, the odds of ever‐use and of consistent use were elevated among females who had discussed contraception with the partner before their first sex together (2.9 and 2.1, respectively), and the odds increased among males as the number of presexual couple‐like activities increased (1.2 for each).

CONCLUSIONS: Teenagers must use contraception consistently over time and across relationships despite pressure not to. Therefore, they must learn to negotiate sexual and contraceptive decisions in each relationship.
A Specific Limbic Circuit Underlies Opiate Withdrawal Memories
Authors: Frenois François , Stinus Luis , Di Blasi Francesco , Cador Martine , Le Moine Catherine
Published: February 2005

Compulsive drug-seeking behavior and its renewal in former drug addicts is promoted by several situations, among which reactivation of drug withdrawal memories plays a crucial role. A neural hypothesis is that such memories reactivate the circuits involved in withdrawal itself and promote a motivational state leading to drug seeking or taking. To test this hypothesis, we have analyzed the neural circuits and cell populations recruited when opiate-dependent rats are reexposed to stimuli previously paired with withdrawal (memory retrieval) and compared them with those underlying acute withdrawal during conditioning (memory formation). Usingin situhybridization for c-fosexpression, we report here that reexposure to a withdrawal-paired environment induced conditioned c-fosresponses in a specific limbic circuit, which can be partially dissociated from the structures involved in acute withdrawal. At the amygdala level, c-fosresponses were doubly dissociated between the central and basolateral (BLA) nuclei, when comparing the two situations. Detailed phenotypical analyses in the amygdala and ventral tegmental area (VTA) show that specific subpopulations in the BLA are differentially involved in the formation and retrieval of withdrawal memories, and strikingly that a population of VTA dopamine neurons is activated in both situations. Together, this indicates that withdrawal memories can drive activity changes in specific neuronal populations of interconnected limbic areas known to be involved in aversive motivational processes. This first study on the neural substrates of withdrawal memories strongly supports an incentive-motivational view of withdrawal in opiate addiction that could be crucial in compulsive drug seeking and relapse.
Altered Ion Channels in an Animal Model of Charcot-Marie-Tooth Disease Type IA
Authors: Devaux Jérôme J. , Scherer Steven S.
Published: February 2005

How demyelination and remyelination affect the function of myelinated axons is a fundamental aspect of demyelinating diseases. We examined this issue inTrembler-Jmice, a genetically authentic model of a dominantly inherited demyelinating neuropathy of humans. The K+channels Kv1.1 and Kv1.2 channels were often improperly located in the paranodal axon membrane, typically associated with improperly formed paranodes, and in unmyelinated segments between internodes. As in wild-type nerves,Trembler-Jnodes contained Nav1.6, ankyrin-G, βIV-spectrin, and KCNQ2, but, unlike wild-type nerves, they also contained Kv3.1b and Nav1.8. In unmyelinated segments bordered by myelin sheaths, these proteins were clustered in heminodes and did not appear to be diffusely localized in the unmyelinated segments themselves. Nodes and heminodes were contacted by Schwann cells processes that did not have the ultrastructural or molecular characteristics of mature microvilli. Despite the presence of Nav1.8, a tetrodotoxin-resistant sodium channel, sciatic nerve conduction was at least as sensitive to tetrodotoxin inTrembler-Jnerves as in wild-type nerves. Thus, the profound reorganization of axonal ion channels and the aberrant expression of novel ion channels likely contribute to the altered conduction inTrembler-Jnerves.
Functional Thalamocortical Synapse Reorganization from Subplate to Layer IV during Postnatal Development in theReeler-Like Mutant Rat (Shaking Rat Kawasaki)
Authors: Higashi Shuji , Hioki Kyoji , Kurotani Tohru , Kasim Nicholas , Molnár Zoltán
Published: February 2005

Transient synapse formation between thalamic axons and subplate neurons is thought to be important in thalamocortical targeting.Shaking rat Kawasaki(SRK), having reversed cortical layering similarly observed inreelermouse, provides an interesting model system to test this idea. The spatial and temporal pattern of excitation was investigated using optical recording with voltage-sensitive dyes in thalamocortical slice preparations from SRK. At postnatal day 0 (P0), a strong optical response was elicited within the superplate of the SRK in the cell layer corresponding to subplate in wild-type (WT) rats. By P3, this response rapidly descended into deep cortical layers comprised of layer IV cells, as identified with 5-bromo-2′-deoxyuridine birthdating at embryonic day 17. During the first 3 postnatal days, both the subplate and cortical plate responses were present, but by P7, the subplate response was abolished. Tracing individual axons in SRK revealed that at P0-P3, a large number of thalamocortical axons reach the superplate, and by P7-P10, the ascending axons develop side branches into the lower or middle cortical layers. Synaptic currents were also demonstrated in WT subplate cells and in SRK superficial cortical cells using whole-cell recording. These currents were elicited monosynaptically, because partial AMPA current blockade did not modify the latencies. These results suggest that the general developmental pattern of synapse formation between thalamic axons and subplate (superplate) neurons in WT and SRK is very similar, and individual thalamic arbors in cortex are considerably remodeled during early postnatal development to find layer IV equivalent neurons.
Neurokininergic Mechanism within the Lateral Crescent Nucleus of the Parabrachial Complex Participates in the Heart-Rate Response to Nociception
Authors: Boscan Pedro , Dutschmann Mathias , Herbert Horst , Paton Julian F. R.
Published: February 2005

We wanted to ascertain whether the lateral parabrachial nucleus was involved in mediating the heart-rate response evoked during stimulation of somatic nociceptors. Reversible inactivation of the lateral parabrachial nucleus, using a GABAAagonist, reduced the reflex tachycardia evoked during noxious (mechanical) stimulation of the forelimb by ∼50%. The same effect was observed after blockade of neurokinin 1 receptors within the lateral parabrachial nucleus, indicating a possible involvement for substance P as a neurotransmitter. Immunocytochemistry revealed a strong expression of substance P-immunoreactive fibers and boutons in all lateral subnuclei, but they were particularly dense in the lateral crescent subnucleus. Histological verification showed that the most effective injection sites for attenuating the noxious-evoked tachycardia were all placed in or near to the lateral crescent nucleus of the lateral parabrachial complex. Many single units recorded from this region were activated by high-intensity brachial nerve stimulation. The brachial nerve evoked firing responses of some of these neurons was reversibly reduced after local delivery of a neurokinin 1 receptor antagonist. However, only a minority of these neurons followed a paired-pulse stimulation protocol applied to the spinal cord, suggesting a predominance of indirect projections from the spinal cord to the parabrachial nucleus. We conclude that the cardiac component of the response to somatic nociception involves indirect spinal pathways that most likely excite neurons located in the lateral crescent nucleus of the parabrachial complex via activation of neurokinin 1 receptors.
Presenilin-1-Dependent Transcriptome Changes
Authors: Mirnics Károly , Korade Zeljka , Arion Dominique , Lazarov Orly , Unger Travis , Macioce Melissa , Sabatini Michael , Terrano David , Douglass Katherine C. , Schor Nina F. , Sisodia Sangram S.
Published: February 2005

Familial forms of Alzheimer's disease (FADs) are caused by the expression of mutant presenilin 1 (PS1) or presenilin 2. Using DNA microarrays, we explored the brain transcription profiles of mice with conditional knock-out ofPS1(cKOPS1) in the forebrain. In parallel, we performed a transcription profiling of the hippocampus and frontal cortex of the FAD-linked ΔE9 mutant transgenic (TG) mice and matched controls [TG mice expressing wild-type humanPS1(hPS1)]. When the TG and cKO datasets were cross-compared, the majority of the 30 common expression alterations were in opposite direction, suggesting that the FAD-linkedPS1variant produces transcriptome changes primarily by gain of aberrant function. Our microarray studies also revealed an unanticipated inverse correlation of transcript levels between the brains of mice that coexpress ΔE9hPS1+ amyloid precursor protein (APP)695Swe and ΔE9hPS1single transgenic mice. The opposite directionality of these changes in transcript levels must be a function of APP and/or APP derivatives.
A Truncated Tropo-Myosine-Related Kinase B Receptor, T1, Regulates Glial Cell Morphology via Rho GDP Dissociation Inhibitor 1
Authors: Ohira Koji , Kumanogoh Haruko , Sahara Yoshinori , Homma Koichi J. , Hirai Hirohisa , Nakamura Shun , Hayashi Motoharu
Published: February 2005

Through tropo-myosine-related kinase B (TrkB) receptors, brain-derived neurotrophic factor (BDNF) performs many biological functions such as neural survival, differentiation, and plasticity. T1, an isoform of TrkB receptors that lacks a tyrosine kinase, predominates in the adult mammalian CNS, yet its role remains controversial. In this study, to examine whether T1 transduces a signal and to determine its function, we first performed an affinity purification of T1-binding protein with the T1-specific C-terminal peptide and identified Rho GDP dissociation inhibitor 1 (GDI1), a GDP dissociation inhibitor of Rho small G-proteins, as a signaling protein directly associated with T1. The binding of BDNF to T1 caused Rho GDI1 to dissociate from the C-terminal tail of T1. Astrocytes cultured for 30 d expressed only endogenous T1 among the BDNF receptors. In 30 d cultured astrocytes, Rho GDI1, when dissociated in a BDNF-dependent manner, controlled the activities of the Rho GTPases, which resulted in rapid changes in astrocytic morphology. Furthermore, using 2 d cultured astrocytes that were transfected with T1, a T1 deletion mutant, or cyan fluorescent protein fusion protein of the T1-specific C-terminal sequence, we demonstrated that T1-Rho GDI1 signaling was indispensable for regulating the activities of Rho GTPases and for the subsequent morphological changes among astrocytes. Therefore, these findings indicate that the T1 signaling cascade can alter astrocytic morphology via regulation of Rho GTPase activity.
Edg8/S1P5: An Oligodendroglial Receptor with Dual Function on Process Retraction and Cell Survival
Authors: Jaillard C. , Harrison S. , Stankoff B. , Aigrot M. S. , Calver A. R. , Duddy G. , Walsh F. S. , Pangalos M. N. , Arimura N. , Kaibuchi K. , Zalc B. , Lubetzki C.
Published: February 2005

Endothelial differentiation gene (Edg) proteins are G-protein-coupled receptors activated by lysophospholipid mediators: sphingosine-1-phosphate (S1P) or lysophosphatidic acid. We show that in the CNS, expression of Edg8/S1P5, a high-affinity S1P receptor, is restricted to oligodendrocytes and expressed throughout development from the immature stages to the mature myelin-forming cell. S1P activation of Edg8/S1P5 on O4-positive pre-oligodendrocytes induced process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway, whereas no retraction was elicited by S1P on these cells derived from Edg8/S1P5-deficient mice. Edg8/S1P5-mediated process retraction was restricted to immature cells and was no longer observed at later developmental stages. In contrast, S1P activation promoted the survival of mature oligodendrocytes but not of pre-oligodendrocytes. The S1P-induced survival of mature oligodendrocytes was mediated through a pertussis toxin-sensitive, Akt-dependent pathway. Our data demonstrate that Edg8/S1P5 activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival and that these effects depend on the developmental stage of the cell.
Bone Formation in the Maxillary Sinus by Using Platelet-rich Plasma: An Experimental Study in Sheep
Authors: Grageda Edgar , Lozada Jaime L. , Boyne Phillip J. , Caplanis Nicholas , McMillan Paul J.
Published: February 2005

Recently, platelet-rich plasma (PRP) has been proven to be an effective regeneration adjunct when combined with autogenous bone in the reconstruction of mandibular defects. However, little is known about the effect of PRP when combined with a bone allograft in the maxillary sinus. The purpose of this study was to quantitatively evaluate the ability of PRP to enhance bone regeneration in the maxillary sinus of sheep when combined with demineralized freeze-dried bone allograft (DFDBA) and cortical cancellous freeze-dried bone allograft (CCFDBA). Ten sheep were selected for bilateral sinus augmentation DFDBA + CCFDBA + PRP (test) and DFDBA + CCFDBA (control). Five were sacrificed at 3 months and the other 5 at 6 months. Hematology tests were performed for platelet count, and histology slides were obtained for histomorphometric analysis taking 2 measures of interest: total area (square millimeters) and percentage of bone fill. Student t tests showed no significant difference between test and control groups for total area (P > .25) and percentage of bone fill (P > .80) at either 3 or 6 months. The control group showed no statistical difference for total area (P < .095) and percentage of bone fill (P < .60) between 3- and 6-month healing times. The test group, however, showed a significant increase in total area (P < .025) but not in percentage of bone fill (P < .40) for the 2 healing periods. When the treatments were compared for interactions within the animal model, no clear tendency was evident for the test group to perform in relation to the control group regarding total area (r = .766, P < .01). A moderate tendency existed between the percentages of bone filled (r = .824, P < .005). Platelet-rich plasma showed higher platelet count than did the whole blood (2 to 5 times). However, no correlation was found between the log ratio and the bone measures. Within the limitations of this study, PRP failed to enhance or accelerate bone regeneration in the maxillary sinus of sheep when combined with bone allograft.
Two Genetically Distinct Forms of Rougheye Rockfish Are Different Species
Authors: Gharrett Anthony J. , Matala Andrew P. , Peterson Eric L. , Gray Andrew K. , Li Zhouzhou , Heifetz Jonathan
Published: February 2005

The variation in mitochondrial DNA (mtDNA) and at eight microsatellite loci was analyzed in 700 rougheye rockfish Sebastes aleutianus sampled along the Pacific Rim from the Oregon coast to the western Aleutian Islands and Bering Sea. The program STRUCTURE was used to analyze the microsatellite genotypes and determine that the samples probably came from two genetically distinct sources (type I and type II) by minimizing the strong Hardy−Weinberg and gametic disequilibria observed in the total sample. The two types had nearly fixed differences at one microsatellite locus (μSma 6), which corresponded to divergent mtDNA haplotype clusters. We conclude that these two types are distinct species. The ranges of the two types overlapped but were not coincident; in some areas, one or the other predominated. For example, most of the Aleutian Island samples were type I fish. Although both types were caught in the same hauls in some regions, often one or the other species was predominant in a haul. The differences in distributions suggest a historic vicariant or ecological basis for their divergence. No phenotypic characteristics have been confirmed that can be used to distinguish the two species visually. Rougheye rockfish have high commercial value and their incidental catch has the potential to greatly affect larger fisheries. The discovery of cryptic speciation in a commercially important species underscores our need to learn more about the distribution and biology of these and other groundfish species.
An investigation of the mechanism of liquid injection into fluidized beds
Authors: Bruhns Stefan , Werther Joachim
Published: February 2005

The mechanism of liquid injection into fluidized bed reactors was investigated by injecting water and ethanol, respectively, into a pilot‐scale bubbling fluidized bed (cross section: 1 × 0.5 m) that was kept at temperatures between 120 and 180°C. Quartz sand and FCC catalyst were used as bed materials. The injected liquid was found to form agglomerates with the bed particles at the nozzle exit and become transported into the bed interior by mixing of the large‐scale solids. There the liquids evaporate from the surface of the particles. © 2005 American Institute of Chemical Engineers AIChE J, 51: 766–775, 2005
Experimental investigation of the hydrodynamics in a liquid–solid riser
Authors: Roy Shantanu , Kemoun Abdenour , Al‐Dahhan M. H. , Dudukovic M. P.
Published: February 2005

Liquid–solid fluid dynamics has been investigated in a 6‐in. (0.15 m) “cold‐flow” circulating fluidized bed riser using non‐invasive flow monitoring methods. Gamma‐ray computed tomography (CT) was used to measure the time‐averaged cross‐sectional solids volume fraction distributions at several elevations. The time‐averaged mean and “fluctuating” solids velocity fields were quantified using the computer‐automated radioactive particle tracking (CARPT) technique. The experimental equipment, protocol of implementation, and data analysis have been discussed briefly, with particular emphasis on the specific features in the use of these techniques for studying high‐density turbulent flows as in a liquid–solid riser. The experimental study examines nine operating conditions, that is, three liquid superficial velocities and three solids flow rates. The solids holdup profile is found to be relatively uniform across the cross section of the riser, with marginal segregation near the walls. The time‐averaged solids velocity profiles are found to have a negative component at the walls, indicating significant solids backmixing. Detailed characterization of the solids velocity fields in terms of RMS velocities, kinetic energies, Hurst exponents, residence time distributions, trajectory length distributions, dispersion coefficients, and so forth are presented. Comparative and symbiotic analyses of the results were used to develop a coherent picture of the solids flow field. In addition, the work also serves to demonstrate the power and versatility of these flow‐imaging techniques in studying highly turbulent and opaque multiphase systems. © 2005 American Institute of Chemical Engineers AIChE J, 51: 802–835, 2005
Hearing in Drosophila: Development of Johnston's organ and emerging parallels to vertebrate ear development
Authors: Boekhoff‐Falk Grace
Published: February 2005

In this review, I describe recent progress toward understanding the developmental genetics governing formation of the Drosophila auditory apparatus. The Drosophila auditory organ, Johnston's organ, is housed in the antenna. Intriguingly, key genes needed for specification or function of auditory cell types in the Drosophila antenna also are required for normal development or function of the vertebrate ear. These genes include distal‐less, spalt and spalt‐related, atonal, crinkled, nanchung and inactive, and prestin, and their vertebrate counterparts Dlx, spalt‐like (sall), atonal homolog (ath), myosin VIIA, TRPV, and prestin, respectively. In addition, Drosophila auditory neurons recently were shown to serve actuating as well as transducing roles, much like their hair cell counterparts of the vertebrate cochlea. The emerging genetic and physiologic parallels have come as something of a surprise, because conventional wisdom holds that vertebrate and invertebrate hearing organs have separate evolutionary origins. The new findings raise the possibility that auditory organs are more ancient than previously thought and indicate that Drosophila is likely to be a powerful model system in which to gain insights regarding the etiologies of human deafness disorders. Developmental Dynamics 232:550–558, 2005. © 2005 Wiley‐Liss, Inc.
Dissecting JNK signaling, one KKKinase at a time
Authors: Stronach Beth
Published: February 2005

Specificity in signal transduction is essential to ensure distinct and appropriate cellular responses to extracellular cues. Determining the mechanisms that mediate specificity is key to understanding complex cell behaviors in development, when multiple pathways fire simultaneously and individual pathways are used recurrently. Jun kinase (JNK) signal transduction exemplifies a pathway that is used multiple times in animal development and homeostasis. Indeed, molecular genetic analysis of JNK signaling in Drosophila has shown that a core signaling module consisting of Hep (JNKK), Bsk (JNK), and Jun regulates various processes, including tissue morphogenesis, wound repair, stress response, innate immune response, and others. Six putative JNKK kinase (JNKKK) family members are present in the fly genome, which could activate the core module in response to distinct stimuli. The diversity of kinases at this level of the signaling hierarchy could substantially increase the number of possible signals that feed into activation of the core module. Recent studies have described the distinct phenotypic consequences of mutations in three of the genes, Slpr (dMLK), Tak1, and Mekk1. These data, together with Drosophila cell culture and genomic array analyses support the contention that the choice of JNKKK may contribute to signaling specificity in vivo. Whether this is achieved by individual JNKKKs or by means of a combinatorial mechanism will require a systematic characterization of compound mutants and a toolbox of transcriptional reporters specific for distinct JNK‐dependent processes. Developmental Dynamics 232:575–584, 2005. © 2005 Wiley‐Liss, Inc.
Setting the stage for development: mRNA translation and stability during oocyte maturation and egg activation in Drosophila
Authors: Tadros Wael , Lipshitz Howard D.
Published: February 2005

Early animal development is controlled by maternally encoded RNAs and proteins, which are loaded into the egg during oogenesis. Oocyte maturation and egg activation trigger changes in the translational status and the stability of specific maternal mRNAs. Whereas both maturation and activation have been studied in depth in amphibians and echinoderms, only recently have these processes begun to be dissected using the powerful genetic and molecular tools available in Drosophila. This review focuses on the mechanisms and functions of regulated maternal mRNA translation and stability in Drosophila—and compares these mechanisms with those elucidated in other animal models, particularly Xenopus—beginning late in oogenesis and continuing to the mid‐blastula transition, when developmental control is transferred to zygotically synthesized transcripts. Developmental Dynamics 232:593–608, 2005. © 2005 Wiley‐Liss, Inc.
Amnioserosa is required for dorsal closure in Drosophila
Authors: Scuderi Anne , Letsou Anthea
Published: February 2005

Dorsal closure in the fruit fly Drosophila melanogaster is a complex morphogenetic process, driven by sequential signaling cascades and involving multiple forces, which contribute to cell movements and rearrangements as well as to changes in cell shape. During closure, lateral epidermal cells elongate along the dorsoventral axis and subsequently spread dorsally to cover the embryonic dorsal surface. Amnioserosal cells, which are the original occupants of the most dorsal position in the developing embryo, constrict during closure; thus, the increase in epidermal surface area is accommodated by a reduction in the amnioserosal surface area. Several of the epidermal requirements for closure have been established in functional assays. In contrast, amnioserosal requirements for closure have remained elusive, in part because laser ablation and clonal approaches are limited to only subsets of amnioserosal cells. Here, we report our use of the UAS‐GAL4 system to target expression of the cell autonomous toxin Ricin‐A to all cells of the amnioserosa. We show that ablation of the amnioserosa leads to clear defects in dorsal closure and, thus, directly demonstrate a role for the amnioserosa in dorsal closure. We also show that DJNK (Drosophila Jun N‐terminal kinase) signaling, an epidermal trigger of closure, is unaffected by amnioserosal ablation. These data, together with our demonstration that amnioserosal ablated and Dpp signaling mutant embryos exhibit shared loss‐of‐function phenotypes, point to a requirement for the amnioserosa in dorsal closure that is downstream of Dpp, perhaps as part of a paracrine response to this signaling cascade. Developmental Dynamics 232:791–800, 2005. © 2005 Wiley‐Liss, Inc.
Novel dominant‐negative mutation within the six domain of the conserved eye specification gene sine oculis inhibits eye development in Drosophila
Authors: Roederer Kristin , Cozy Loralyn , Anderson Jason , Kumar Justin P.
Published: February 2005

The development of the compound eye of Drosophila is controlled, in part, by the concerted actions of several nuclear proteins that form an intricate regulatory system. One member of this network is sine oculis (so), the founding member of the Six gene family. Mutations within so affect the entire visual system, including the compound eye. The vertebrate homologs Six3 and Six6 also appear to play crucial roles in retinal formation. Mutations in Six3 inhibit retinal formation in chickens and fish, whereas those in Six6 are the underlying cause of bilateral anophthalmia in humans. Together, these phenotypes suggest a conserved role for the Six genes in eye development. In this report, we describe the effects of a dominant‐negative mutation of sine oculis on the development of the compound eye of Drosophila. The mutation resides within the Six domain and may have implications for eye development and disease. Developmental Dynamics 232:753–766, 2005. © 2005 Wiley‐Liss, Inc.
Simulated annealing search through general structure floor plans using sequence‐pair
Authors: Kiyota Koji , Fujiyoshi Kunihiro
Published: February 2005

In VLSI layout design, a “floor plan” is often derived prior to solving the placement problem. The floor plan is obtained by dividing the square representing the chip into several rectangular rooms, to which modules are assigned, and then the locations of the module and interconnects are approximately determined. In floor plan study, the use of slice structures is common. Recently, however, a method of converting the sequence‐pair, as a representation of the rectangular packing, to the floor plan has been proposed. Hence, it is now possible to list all floor plans with general configurations including the nonslice structure. However, in such a method there is the deficiency that an “empty room” without an assigned module may be generated. In the present paper, an adjacent solution is proposed for effective search of only the general configuration floor plan without empty rooms by using the simulated annealing method. An ingenious technique for effectively deriving this adjacent solution is described. The diameter of this solution space is proven to be of polynomial size. Also, the proposed solution space is experimentally compared with the solution space of slice structures. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(6): 28–38, 2005; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecjc.10003
Anti‐HER‐3 MAbs inhibit HER‐3‐mediated signaling in breast cancer cell lines resistant to anti‐HER‐2 antibodies
Authors: van der Horst Edward Htun , Murgia Marta , Treder Martin , Ullrich Axel
Published: February 2005

Two members of the EGF receptor family, HER2 and HER3, act as key oncogenes in breast cancer cells. A MAb against HER2, trastuzumab, interferes with HER2 signaling and istherapeutically effective in humans. Here, we explored the biologic effects of an antibody against HER3 (α‐HER3ECD) in the invasive breast cancer cell lines MCF‐7ADR and MDA‐MB‐468. Pretreating the breast cancer cells with α‐HER3ECD prior to Heregulin stimulation caused significant reduction of the migratory and proliferative properties. This reduction is due to a substantial decrease in the tyrosine phosphorylation content of HER2 and to a modification of the HER2/HER3 association, which ultimately inhibits the activity of the downstream effectors phosphatidyinositol‐3‐OH‐kinase and c‐jun‐terminal kinase. Furthermore, HER3 is internalized and not activated by HRG after pretreatment with α‐HER3ECD. Our data reinforce the notion that HER3 could be a key target in cancer drug design and show the great potential of anti‐HER3 antibodies for the therapy of breast cancer and other malignancies characterized by overexpression of HER3. © 2005 Wiley‐Liss, Inc.
Tumor‐specific CD4+ T cells from a patient with renal cell carcinoma recognize diverse shared antigens
Authors: Mautner Josef , Jaffee Elizabeth M. , Pardoll Drew M.
Published: February 2005

Murine models for immune‐mediated tumor regression have defined an essential role for CD4+ T helper (Th) cells, but the contribution of these cells to antitumoral immune responses in humans remains poorly defined. Here, we investigated the Th cell response against the autologous tumor in a patient with metastasized renal cell carcinoma (RCC) exhibiting objective clinical response to immunotherapy. Peripheral blood T cells of the patient were repeatedly stimulated in vitro using either autologous IFNγ‐treated whole tumor cells or Epstein‐Barr virus‐immortalized B cells (EBV‐B) pulsed with tumor cell lysate. CD4+ T‐cell clones recognizing autologous tumor cells but not EBV‐B cells were efficiently reactivated and expanded with both types of stimulator cells, establishing the latter as potentially useful for isolating CD4+ T cells reactive against MHC class II‐negative tumors. Two T‐cell clones from both stimulation protocol were further characterized. The restricting MHC class II molecules were defined by using allogeneic EBV‐B cells pulsed with tumor lysate, and the expression pattern of the antigens was examined by analyzing lysates from normal kidney cells, allogeneic RCCs as well as tumors of different histologic origin. Furthermore, the subcellular localization of the antigens recognized by the T‐cell clones was examined by fractionating the tumor lysate, and the Th phenotype was determined by assessing the cytokines released after T cell activation. These experiments show that a dual Th1/Th2, MHC class II‐restricted T‐helper‐cell response against diverse shared tumor antigens has been elicited in this patient. © 2005 Wiley‐Liss, Inc.
CpG island methylation in aberrant crypt foci and cancers from the same patients
Authors: Luo Liping , Chen Wei‐dong , Pretlow Theresa P.
Published: February 2005

Aberrant methylation of CpG islands is a common alteration in human colon cancer. Methylation of only a limited number of loci has been studied in aberrant crypt foci (ACF), the earliest identified premalignant lesions in the colon, and in only a limited number of lesions from the same patients. Methylation‐specific PCR was used to analyze 35 ACF, samples of normal crypts with the same number of crypts as were in each ACF and 22 cancers from the same patients. Aberrant methylation in cellular retinol‐binding protein 1 (CRBP1), MINT31 or H‐cadherin (CDH13) was identified in 19 of 35 (54%) ACF. Hypermethylation of CRBP1, MINT31 or CDH13 was more frequent (15 of 22, 68%) in cancers. DNA methylation of CRBP1, MINT31 or CDH13 was not correlated between cancers and ACF from the same patients. Aberrant methylation was not correlated with patient age, number of crypts in the ACF or cancer stage. These results suggest that hypermethylation in the promoter region of some genes is an independent event, occurs early in human colon tumorigenesis and may play an important role during the transformation and progression of some lesions to colon cancers. © 2005 Wiley‐Liss, Inc.
Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors
Authors: Tischoff Iris , Markwarth Annett , Witzigmann Helmut , Uhlmann Dirk , Hauss Johann , Mirmohammadsadegh Alireza , Wittekind Christian , Hengge Ulrich R. , Tannapfel Andrea
Published: February 2005

Previously, the RASSF1A, BLU and SEMAPHORIN 3B (SEMA3B) candidate tumor suppressor genes on chromosome 3p21.3 were found to be inactivated and downregulated by genetic and epigenetic changes in lung cancer. We analyzed the methylation status of RASSF1A, BLU and SEMA3B in 35 hepatocellular carcinomas (HCCs) and 15 cholangiocarcinomas (CCs) by methylation‐specific PCR and loss of heterozygosity (LOH) at 3p21.3 after microdissection. The presence of mRNA transcripts was confirmed by semiquantitative PCR. SEMA3B hypermethylation was found in 29/35 HCCs (83%) and in all (15/15) patients with CC. BLU promoter hypermethylation was detected in 7/35 (20%) HCCs and 3/15 (20%) CCs. In 2 corresponding specimens of hepatitis B virus‐related liver cirrhosis, BLU methylation was also observed, but not in uninvolved normal liver tissue. RASSF1A was methylated in 21/35 HCCs (60%) and in 10/15 CCs (67%). LOH at 3p21.3 occurred in 8/35 (23%) HCCs and 3/15 (20%) CCs. The presence of hypermethylation was statistically associated with LOH of SEMA3B and correlated with downregulation of mRNA transcripts. SEMA3B transcripts increased upon treatment of HCC cell lines with the demethylation compound 5‐aza‐2‐deoxycytidine. In conclusion, our data indicate that 2‐hit gene silencing of SEMA3B through epigenetic changes and allele loss is a common and important event in the carcinogenesis of malignant liver tumors. © 2005 Wiley‐Liss, Inc.