bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing dielectric relaxation properties of liquid CS2 with terahertz time-domain spectroscopy
Authors: Yu B. L. , Zeng F. , Xing Q. , Alfano R. R.
Published: June 2003

Terahertz time-domain spectroscopy is used to investigate the dielectric relaxation properties of liquid CS2. The frequency-dependent absorption coefficient and index of refraction were measured in the frequency range 0.2–2.0 THz. The ultrafast dielectric relaxation time of liquid CS2 was determined to be 630±30 fs by fitting the dielectric function to the Debye model which is attributed to average time for rocking and rotational response of the CS2 molecules possessing an anisotropic polarizability.
Thermoelastic stress in GaAs/AlGaAs quantum cascade lasers
Authors: Spagnolo Vincenzo , Scamarcio Gaetano , Marano Danilo , Page Hideaki , Sirtori Carlo
Published: June 2003

We have determined the shear stress associated with the temperature gradient in quantum cascade lasers operated in continuous-wave mode. This information was obtained as a function of the electrical power using a combination of microprobe photoluminescence and anti-Stokes/Stokes Raman measurements in ridge-waveguide GaAs structures mounted epilayer down to the heat sink. At electrical power densities in the order of ∼5 kW/cm2, the strain in the cladding layers at the edges of the laser ridges reaches the critical value for the creation of misfit dislocations. Above 10–12 kW/cm2, extended defect formation and eventual device failure are observed.
Self-assembled growth of single-walled carbon nanotubes by pyrolysis of metalorganic precursor
Authors: Harutyunyan A. R. , Chen G. , Eklund P. C.
Published: June 2003

Carbon nanotubes with controllable diameters from ∼1 to 200 nm were synthesized by pyrolysis of iron phthalocyanine at ∼900 °C under argon gas flow. Diameters of nanotubes were controlled by varying the metal concentration, using the solid phase dilution of iron phthalocyanine with metal-free phthalocyanine to various degrees. Self-assembled single-walled carbon nanotubes were obtained by using iron phthalocyanine precursor diluted with metal-free phthalocyanine in 1:24 molar ratio.
Two-photon absorption and multiphoton-induced photoluminescence of bulk GaN excited below the middle of the band gap
Authors: Toda Y. , Matsubara T. , Morita R. , Yamashita M. , Hoshino K. , Someya T. , Arakawa Y.
Published: June 2003

Optical nonlinearity in the yellow luminescence (YL) band of GaN was investigated using thick bulk samples. Transient pump–probe measurements revealed strong transmission changes due to two-photon absorption (TPA) even at the middle of the YL band. The TPA coefficient evaluated reaches ∼5 cm/GW at about 1.3 eV, which was as large as the mid-gap resonance. The TPA spectrum clearly showed that the observed large nonlinearity originated from the YL band. On the basis of efficient TPA in the YL band, relaxation processes in the multiphoton-induced photoluminescence excitation spectrum were also investigated.
Dual-mode mechanical resonance of individual ZnO nanobelts
Authors: Bai X. D. , Gao P. X. , Wang Z. L. , Wang E. G.
Published: June 2003

The mechanical resonance of a single ZnO nanobelt, induced by an alternative electric field, was studied by in situ transmission electron microscopy. Due to the rectangular cross section of the nanobelt, two fundamental resonance modes have been observed corresponding to two orthogonal transverse vibration directions, showing the versatile applications of nanobelts as nanocantilevers and nanoresonators. The bending modulus of the ZnO nanobelts was measured to be ∼52 GPa and the damping time constant of the resonance in a vacuum of 5×10−8 Torr was ∼1.2 ms and quality factor Q=500.
Synthesis and optical properties of S-doped ZnO nanowires
Authors: Geng B. Y. , Wang G. Z. , Jiang Z. , Xie T. , Sun S. H. , Meng G. W. , Zhang L. D.
Published: June 2003

S-doped ZnO nanowires with an average diameter of 80 nm and length up to several tens of micrometers were produced through a simple physical evaporation approach. The nanowires had a single-crystal hexagonal structure and grew along the [102] direction. Photoluminescence (PL) measurements showed that the doping of sulfur shifted the PL spectrum peak towards short wavelengths, and the doping quantity was found responsible for the different characteristics.
Normalized method for comparing tensile behaviors of electrorheological fluids
Authors: Tian Yu , Zou Qian
Published: June 2003

Tensile behaviors of electrorheological (ER) fluids over a wide applied field range have been determined. Normalized tensile stress and the normalized electric field have been proposed to compare the elongations of ER fluids under different conditions. This clearly showed the nature of the stress-strain curves under different initial electric fields and the structure effect during the elongations. Corresponding to the tensile behavior change, the exponent of tensile yield stress versus electric field was also found to vary in different initial field range.
Ferroelectric field-effect transistor with a SrRuxTi1−xO3 channel
Authors: Schrott A. G. , Misewich J. A. , Nagarajan V. , Ramesh R.
Published: June 2003

A ferroelectric field-effect transistor with a SrRuxTi1−xO3 solid-solution channel layer and a lead zirconate titanate gate oxide has been fabricated. The remnant polarization of the ferroelectric yields two states at 0 V, which produce a relative change in channel resistance (ΔR/R) of 75% and a coercivity of 3 V. The channel has sufficient off-state free carrier concentration to provide sufficient balancing charge for ferroelectric stability. The device was subjected to more than 1010 read-write cycles with no degradation. This nonvolatile device offers the possibility of a nondestructive, current sense memory cell with good retention properties.
Conotoxins as Sensors of Local pH and Electrostatic Potential in the Outer Vestibule of the Sodium Channel
Authors: Hui Kwokyin , McIntyre Deane , French Robert J.
Published: June 2003

We examined the block of voltage-dependent rat skeletal muscle sodium channels by derivatives of μ-conotoxin GIIIA (μCTX) having either histidine, glutamate, or alanine residues substituted for arginine-13. Toxin binding and dissociation were observed as current fluctuations from single, batrachotoxin-treated sodium channels in planar lipid bilayers. R13X derivatives of μCTX only partially block the single-channel current, enabling us to directly monitor properties of both μCTX-bound and -unbound states under different conditions. The fractional residual current through the bound channel changes with pH according to a single-site titration curve for toxin derivatives R13E and R13H, reflecting the effect of changing the charge on residue 13, in the bound state. Experiments with R13A provided a control reflecting the effects of titration of all residues on toxin and channel other than toxin residue 13. The apparent pKs for the titration of residual conductance are shifted 2–3 pH units positive from the nominal pK values for histidine and glutamate, respectively, and from the values for these specific residues, determined in the toxin molecule in free solution by NMR measurements. Toxin affinity also changes dramatically as a function of pH, almost entirely due to changes in the association rate constant, kon. Interpreted electrostatically, our results suggest that, even in the presence of the bound cationic toxin, the channel vestibule strongly favors cation entry with an equivalent local electrostatic potential more negative than −100 mV at the level of the “outer charged ring” formed by channel residues E403, E758, D1241, and D1532. Association rates are apparently limited at a transition state where the pK of toxin residue 13 is closer to the solution value than in the bound state. The action of these unique peptides can thus be used to sense the local environment in the ligand-–receptor complex during individual molecular transitions and defined conformational states.
Designing effective leadership interventions: a case study of vocational education and training
Authors: Falk Ian
Published: June 2003

The paper reports on research into effective leadership interventions. The findings and conclusions are derived from 12 diverse vocational education and training (VET) sites around Australia. Data are from 44 written survey and interview responses and five focus groups yielding a total of 64 respondents. The main finding is a four‐stage cycle of effective leadership interventions and is demonstrated through a case of enabling leadership. The study incorporates context‐dependent profiles of different leaders’ attributes at each of the four stages of the leadership intervention cycle. The research generates new theory and knowledge in an area of leadership research. That is, it is found that the traits and attributes of individual leaders are necessary but not sufficient to explain how to achieve effective and enabling leadership.
“Learnership” in complex organisational textures
Authors: Cooksey Ray W.
Published: June 2003

This paper focuses on developing an integrative view of leadership and organisational learning in the context of dynamic and non‐linear organisational complexity. The outcome of this development is a new conceptualisation termed “learnership”. The concept and process of “learnership” is seen as an evolving meld of leadership and learning where responsibility for learning and for leading is progressively diffused from a few central individuals to a critical mass of organisational members, all of whom become mutually embedded in the learning process, leading where needed, following where needed, but always with a sensitive eye on the complex texture of the learning environment they inhabit. The usefulness of the concept of “learnership” for organisations is discussed and some diagnostic trigger questions for sensing readiness and capability for “learnership” diffusion are presented.
Radical change: a conceptual model for research agendas
Authors: McAdam Rodney
Published: June 2003

The aim of this paper is to conceptualise the metamorphosis when radical or large‐scale change occurs in an organisation. Furthermore, a conceptual model is developed which can act as a mechanism for developing further research agendas in this area. There are many methodologies, tools and techniques for developing change at all levels of magnitude in organisations. An example at the large‐scale level of change is Business Process Reengineering. The literature reveals that the transforming element of these methodologies is ill defined and its “black box” effect adds to the mysticism, which surrounds many of these methods. If this transforming element, which results in large‐scale change, can be conceptualised and outlined in a conceptual model, then a means of conducting further research is provided. Also, further definition should enable more successful large‐scale change interventions to be made in organisations. Outlines a conceptual model based on a critique of the literature. The key factors in the model are creativity, vision, benchmarking and information technology.
A framework for separation of duties in an SAP R/3 environment
Authors: Little Adam , Best Peter J.
Published: June 2003

The majority of medium‐to‐large international organizations have adopted enterprise resource planning systems (ERPs) of which SAP R/3 is the current market leader. This paper proposes a framework for the separation of duties in SAP R/3. Separation of duties is viewed as a critical component of an organization’s internal control structure aimed primarily at reducing opportunities for fraudulent activities. R/3 assigns profiles consisting of authorizations to users. Accordingly, R/3 facilitates the implementation of “role‐based access control”, where these profiles may be designed consistent with organizational roles and assigned to users performing these roles. This paper proposes a framework for adequate separation of duties using a role‐based approach in the financial accounting (FI) module of the R/3 system. Case studies were undertaken to refine the framework and to explore its application in a practical environment. This empirical research provided support for the adequacy of the proposed framework.
Atmospheric Detection of Water Dimers via Near-Infrared Absorption
Authors: Pfeilsticker K. , Lotter A. , Peters C. , Bösch H.
Published: June 2003

Weakly bonded pairs of water molecules (H
2
O)
2
, or water dimers (WDs), may play an important role in photochemistry and climate, but the overlap of most of its spectral features with the water monomer (WM) has made detection difficult. We report on WD absorption measurements by means of atmospheric long-path (18.34 kilometers) differential optical absorption spectroscopy of the near-infrared OH stretching mode |0>
f
|4>
b
overtone transition predicted to be located near 746 nanometers. Our observation is in reasonable agreement with the known thermochemistry, calculated and measured structure, and spectroscopy (band strength, shape, and width) of the WD. The observation implies that the WD |0>
f
|4>
b
band is located at 749.5 nanometers, with a full width at half maximum of ∼19.4 wave numbers, and that its band strength ranges between 1.23 × 10
–
22
and 5.25 × 10
–
22
centimeters per molecule.
Molecular Ordering of Organic Molten Salts Triggered by Single-Walled Carbon Nanotubes
Authors: Fukushima Takanori , Kosaka Atsuko , Ishimura Yoji , Yamamoto Takashi , Takigawa Toshikazu , Ishii Noriyuki , Aida Takuzo
Published: June 2003

When mixed with imidazolium ion-based room-temperature ionic liquid, pristine single-walled carbon nanotubes formed gels after being ground. The heavily entangled nanotube bundles were found to untangle within the gel to form much finer bundles. Phase transition and rheological properties suggest that the gels are formed by physical cross-linking of the nanotube bundles, mediated by local molecular ordering of the ionic liquids rather than by entanglement of the nanotubes. The gels were thermally stable and did not shrivel, even under reduced pressure resulting from the nonvolatility of the ionic liquids, but they would readily undergo a gel-to-solid transition on absorbent materials. The use of a polymerizable ionic liquid as the gelling medium allows for the fabrication of a highly electroconductive polymer/nanotube composite material, which showed a substantial enhancement in dynamic hardness.
Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition
Authors: Calarese Daniel A. , Scanlan Christopher N. , Zwick Michael B. , Deechongkit Songpon , Mimura Yusuke , Kunert Renate , Zhu Ping , Wormald Mark R. , Stanfield Robyn L. , Roux Kenneth H. , Kelly Jeffery W. , Rudd Pauline M. , Dwek Raymond A. , Katinger Hermann , Burton Dennis R. , Wilson Ian A.
Published: June 2003

Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus type 1 (HIV-1) isolates by binding an unusually dense cluster of carbohydrate moieties on the âsilentâ face of the gp120 envelope glycoprotein. Crystal structures of Fab 2G12 and its complexes with the disaccharide ManÎ±1-2Man and with the oligosaccharide Man
9
GlcNAc
2
revealed that two Fabs assemble into an interlocked V
H
domain-swapped dimer. Further biochemical, biophysical, and mutagenesis data strongly support a Fab-dimerized antibody as the prevalent form that recognizes gp120. The extraordinary configuration of this antibody provides an extended surface, with newly described binding sites, for multivalent interaction with a conserved cluster of oligomannose type sugars on the surface of gp120. The unique interdigitation of Fab domains within an antibody uncovers a previously unappreciated mechanism for high-affinity recognition of carbohydrate or other repeating epitopes on cell or microbial surfaces.
Hexameric Structure and Assembly of the Interleukin-6/IL-6 α-Receptor/gp130 Complex
Authors: Boulanger Martin J. , Chow Dar-chone , Brevnova Elena E. , Garcia K. Christopher
Published: June 2003

Interleukin-6 (IL-6) is an immunoregulatory cytokine that activates a cell-surface signaling assembly composed of IL-6, the IL-6 α-receptor (IL-6Rα), and the shared signaling receptor gp130. The 3.65 angstrom–resolution structure of the extracellular signaling complex reveals a hexameric, interlocking assembly mediated by a total of 10symmetry-related, thermodynamically coupled interfaces. Assembly of the hexameric complex occurs sequentially: IL-6 is first engaged by IL-6Rα and then presented to gp130in the proper geometry to facilitate a cooperative transition into the high-affinity, signaling-competent hexamer. The quaternary structures of other IL-6/IL-12 family signaling complexes are likely constructed by means of a similar topological blueprint.
Use of hermeneutic research in understanding the meaning of desire for euthanasia
Authors: Mak Yvonne , Elwyn Glyn
Published: June 2003

The philosophy of palliative care is holistic, paying attention to the multidimensional needs of the terminally ill in promoting quality of life and relieving suffering. These needs have to be viewed within their cultural, temporal and social contexts. Thus in conducting patient need-based research, the patients' perspectives are vital data in providing intimate insight into the core issues of any phenomenon under study. This paper aims to illustrate the usefulness of hermeneutic philosophy in palliative care research, as demonstrated in a study to understand the meaning of desire for euthanasia directly from the terminally ill. Two particular aspects of the study are emphasized, namely the research methodology and research process, rather than its findings regarding the meaning of desire for euthanasia. Hermeneutic philosophy parallels that of palliative care, as it also values human experience and social contexts. This approach allows in-depth understanding into a phenomenon in a humane and holistic manner, with adherence to methodological and scientific rigour. The process of hermeneutic interpretation can also promote evidence-based reflective practice. The adoption of a hermeneutic attitude in clinical practice can refine professional self-development in the art of communication and caring.
Mental health of looked after children
Authors: Richardson Joanna , Lelliott Paul
Published: June 2003

Looked after children are disadvantaged with regard to their mental and physical health and education. Research is limited on this population, but dramatic findings prompted the Government to produce a number of guidance and policy documents over the past 5 years. This paper discusses the available research and highlights the problems that looked after children face. The new policy initiatives are listed, along with a number of obstacles to be overcome if the care of these young people is to be improved.
Increasing the trust in scientific authorship
Authors: Lagnado Max
Published: June 2003

The system of scientific authorship is based on trust. Journal editors, reviewers and readers expect that a paper's content reflects the opinions of the authors and all the available data. Recently, there has been concern that this trust may be undermined by the involvement of industry-paid writers in the preparation of publications (Bodenheimer, 2000). These professional writers are either employed directly by pharmaceutical companies or work for medical communications agencies; their contribution to a paper varies, but may include writing the first draft of a manuscript for the authors to revise or editing a paper written by the authors (Lagnado, 2003). Despite much discussion about the merits of industry-funded writing assistance, there has been little research into its effects on the biomedical literature.
Institutionalisation and schizophrenia in Japan: Social environments and negative symptoms
Authors: Oshima Iwao , Mino Yoshio , Inomata Yoshimasa
Published: June 2003

Background

The number of psychiatric beds per capita in Japan is the highest in the world, and a replication of earlier British research is needed to identify possible means of improving the mental health system.

Aims

To describe the current situation of psychiatric hospitals in Japan and to examine the relationship between negative symptoms of schizophrenia and social environments.

Method

In-patients with schizophrenia were randomly selected from 139 hospitals. Data were obtained for 2758 participants using several scales, including the Manchester Scale and social environment scales.

Results

Negative symptom scales showed a significant correlation with under stimulating social environments in hospitals.

Conclusions

This study confirms the results from the UK and provides evidence for the importance of community-based care and for providing more-stimulating rehabilitation environments.
Serious Incident Inquiries: a survival kit for psychiatrists
Authors: Salter Mark
Published: June 2003

Since 1999, a formal external inquiry into every homicide committed by a person with a mental disorder has been mandatory in the UK (Department of Health, 1994). Common opinion among psychiatrists is that Serious Incident Inquiries are unhelpful as they all reach similar conclusions, add nothing to our current knowledge and do more harm than good in terms of adverse publicity for mental health services (Buchanan, 1999). Despite this, there is presently little sign of a change in public policy. Psychiatrists continue to face the fact that the next incident could be ‘the one that's coming here’. Although the many flaws of the inquiry process have been well described (Szmukler, 2000), few have interpreted this knowledge in a way that is of practical help to a psychiatrist facing an inquiry.
Newspaper coverage of psychiatry and general medicine: comparing tabloids with broadsheets
Authors: Pieters Guido , De Gucht Véronique , Kajosch Hendrik
Published: June 2003

Aims and Method

To study whether psychiatry received differing treatment in newspapers than the other medical specialities, and whether tabloids were more negative in their coverage of general medicine and psychiatry than broadsheets. We conducted a survey of all headlines in all daily newspapers in the Dutch-speaking part of Belgium over a one-month period and judged whether the content was essentially positive, neutral or negative.

Results

There was no significant difference between articles on general medicine and psychiatry with respect to the tone of the article. Whereas negative articles about medicine focused on both doctor and patient to the same extent, negative articles on psychiatry tended more often to describe the patient. Broadsheets published more negative than positive articles, while tabloids published an equal proportion of negative and positive articles.

Clinical Implications

There appears to be no difference in tone with respect to articles on general medicine and psychiatry, respectively. Nevertheless, the fact that negative articles on psychiatry tend to focus more exclusively on the patient points towards continuing stigmatisation of the psychiatric patient. Finally, broadsheets tend to be more negative in covering both general medicine and psychiatry, which contrasts with earlier findings.
Sub-optimal prescribing in an adult community mental health service: prevalence and determinants
Authors: Meagher David , Moran Maria
Published: June 2003

Aims and Method

To compare prescribing practice in a community mental health service with evidence-based guidelines and identify factors related to sub-optimal prescribing. All current patients (n=640) were assessed regarding six key aspects of prescribing (polypharmacy, high-dose treatment, use of thioridazine/maintenance benzodiazepine/maintenance hypnotic or routine anticholinergic treatment). The relationship of quality of prescribing practice to demographic, illness and service variables was examined by regression analysis.

Results

Five-hundred and five (79%) patients were receiving psychotropic medication. Of these, 232 (46%) had evidence of sub-optimal prescribing practice. Mean prescribing practice quality score was 0.75 ± 0.99. Maintenance benzodiazepine/ hypnotic (31%) and anticholinergic (30%) use were particularly common. Prescribing practice quality score was higher in those receiving depot antipsychotic treatment (P < 0.01) and in older patients (P < 0.01). Scores were significantly lower in patients whose principal medical contacts were with a consultant rather than a junior doctor (P < 0.001).

Clinical Implications

Prescribing practices in real-world settings frequently deviate from evidence-based guidelines. The quality of prescribing is related to patient, illness and service variables. In particular, greater contact with consultant staff is linked to better practices. Patients receiving depot antipsychotics are especially liable to less judicious prescribing practice.
Forensic psychiatry in Russia – the links with Britain evolve further
Authors: Gordon Harvey , Meux Clive
Published: June 2003

The perception of forensic psychiatry in Russia has been affected by the abuse of psychiatry for the detention of political dissidents during the later Soviet period (Smith & Oleszczuk, 1996). The Royal College of Psychiatrists played a key role in sanctioning the Soviet Society of Psychiatrists, but reintegration of Russian psychiatry into the international community of psychiatry now seems to be well underway.
International Expert Panel on the Use of Primary (Preoperative) Systemic Treatment of Operable Breast Cancer: Review and Recommendations
Authors: Kaufmann Manfred , von Minckwitz Gunter , Smith Roy , Valero Vicente , Gianni Luca , Eiermann Wolfgang , Howell Anthony , Costa Serban Dan , Beuzeboc Philippe , Untch Michael , Blohmer Jens-Uwe , Sinn Hans-Peter , Sittek Rolf , Souchon Rainer , Tulusan Augustinos H. , Volm Tanja , Senn Hans-Jörg
Published: June 2003

Primary systemic therapy (PST) represents the standard of care in patients with locally advanced breast cancer. In addition, there is increasing information on PST in operable breast disease that supports the use of PST in routine practice. However, current regimens and techniques vary. To address this concern, a group of representatives from breast cancer clinical research groups in France, Germany, Italy, the United Kingdom, and the United States reviewed all available data on prospective randomized trials in this setting. Recommendations are made regarding terminology, indications, regimen, diagnosis before treatment, monitoring of efficacy, tumor localization, surgery, pathologic evaluation, and postoperative treatment.
Interobserver and Intraobserver Variability in Measurement of Non–Small-Cell Carcinoma Lung Lesions: Implications for Assessment of Tumor Response
Authors: Erasmus Jeremy J. , Gladish Gregory W. , Broemeling Lyle , Sabloff Bradley S. , Truong Mylene T. , Herbst Roy S. , Munden Reginald F.
Published: June 2003

Purpose: Response of solid malignancies to therapy is usually determined by serial measurements of tumor size. The purpose of our study was to assess the consistency of measurements performed by readers evaluating lung tumors.

Materials and Methods: The study group was composed of 33 patients with lung tumors more than 1.5 cm. Bidimensional (BD) and unidimensional (UD) measurements were performed on computed tomography (CT) scans according to the World Health Organization (WHO) criteria and the Response Evaluation Criteria in Solid Tumors (RECIST), respectively. Measurements were performed independently by five thoracic radiologists using printed film and were repeated after 5 to 7 days. Inter- and intraobserver measurement variations were estimated through statistical modeling.

Results: There were 40 tumors with an average size of 1.8 to 8.0 cm (mean, 4.1 cm). Analysis of variance showed a significant difference (P < .05) among readers and among the measured nodules for UD and BD measurements. Interobserver misclassification rates were more than intraobserver misclassification rates using either progressive disease or response criteria. The probability of misclassifying a tumor with the WHO criteria or RECIST was greatest with interobserver measurements when criteria for progression (43% BD, 30% UD) were used and lowest with intraobserver measurements when criteria for response (2.5% BD, 3.0% UD) were used. In addition, interobserver misclassification rates were more than intraobserver misclassification rates for both regular and irregular tumors.

Conclusion: Measurements of lung tumor size on CT scans are often inconsistent and can lead to an incorrect interpretation of tumor response. Consistency can be improved if the same reader performs serial measurements for any one patient.
Effects of Radiotherapy on Cognitive Function in Patients With Low-Grade Glioma Measured by the Folstein Mini-Mental State Examination
Authors: Brown Paul D. , Buckner Jan C. , O’Fallon Judith R. , Iturria Nancy L. , Brown Cerise A. , O’Neill Brian P. , Scheithauer Bernd W. , Dinapoli Robert P. , Arusell Robert M. , Curran Walter J. , Abrams Ross , Shaw Edward G.
Published: June 2003

Purpose: To assess the neurocognitive effects of cranial radiotherapy on patients with low-grade gliomas, we analyzed cognitive performance data collected in a prospective, intergroup clinical trial.

Methods: Patients included 203 adults with supratentorial low-grade gliomas randomly assigned to a lower dose (50.4 Gy in 28 fractions) or a higher dose (64.8 Gy in 36 fractions) of localized radiotherapy. Folstein Mini-Mental State Examination (MMSE) scores and neurologic function scores (NFS) at baseline and key evaluations were analyzed. Median follow-up was 7.4 years in 101 patients still alive. A change of more than three MMSE points was considered clinically significant.

Results: In patients without tumor progression, significant deterioration from baseline occurred at years 1, 2, and 5 in 8.2%, 4.6%, and 5.3% of patients, respectively. Most patients with an abnormal baseline MMSE score (< 27) experienced significant increases. Baseline variables such as radiation dose, conformal versus conventional radiotherapy, number of radiation fields, age, sex, tumor size, NFS, seizures, and seizure medications did not predict cognitive function changes.

Conclusion: In this population, most low-grade glioma patients maintained a stable neurocognitive status after focal radiotherapy as measured by the MMSE. Patients with an abnormal baseline MMSE were more likely to have an improvement in cognitive abilities than deterioration after receiving radiotherapy. Only a small percentage of patients had cognitive deterioration after radiotherapy. However, more discriminating neurocognitive assessment tools may identify cognitive decline not apparent with the use of the MMSE.
Diet and Breast Cancer: Evidence That Extremes in Diet Are Associated With Poor Survival
Authors: Goodwin Pamela J. , Ennis Marguerite , Pritchard Kathleen I. , Koo Jarley , Trudeau Maureen E. , Hood Nicky
Published: June 2003

Purpose: Diet has been postulated to influence breast cancer prognosis; however, existing evidence is weak and inconsistent. Previous studies have sought evidence of a linear relationship between diet and breast cancer outcomes. Because of a U-shaped association of body mass index (BMI) with survival in breast cancer, we hypothesized that a nonlinear association also existed for dietary variables.

Patients and Methods: Four hundred seventy-seven women with surgically resected T1 to T3, N0/1, M0 breast cancer completed the Block Food Frequency Questionnaire 9.3 ± 4.6 weeks (mean ± standard deviation) after diagnosis, reporting intake over the preceding 12 months. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records. A series of Cox models was performed, modeling the association of dietary factors with breast cancer survival linearly and quadratically, adjusting for total energy intake, tumor- and treatment-related variables, and BMI.

Results: Significant nonlinear survival associations were found for protein, oleic acid, cholesterol, polyunsaturated-saturated fat ratio, and for percentage of calories from fat and percentage of calories from carbohydrates in multivariate models. The shape of the survival associations varied across nutrients. Hazard ratios for highest risk quintiles ranged from 2.1 to 6.5. For total fat, adjustment for BMI reduced the multivariate P value obtained from nonlinear Cox models from .05 to .10. No significant linear associations were identified.

Conclusion: The association of key dietary variables with breast cancer survival may be U-shaped rather than linear. Our data suggest that midrange intake of most major energy sources is associated with the most favorable outcomes, and extremes are associated with less favorable outcomes.
Phase II Study of the Efficacy and Tolerability of Two Dosing Regimens of the Farnesyl Transferase Inhibitor, R115777, in Advanced Breast Cancer
Authors: Johnston Stephen R.D. , Hickish Tamas , Ellis Paul , Houston Stephen , Kelland Lloyd , Dowsett Mitch , Salter Janine , Michiels Bart , Perez-Ruixo Juan Jose , Palmer Peter , Howes Angela
Published: June 2003

Purpose: R115777 is an orally active farnesyl transferase inhibitor that specifically blocks farnesylation of proteins involved in growth-factor–dependent cell-signal–transduction pathways. We conducted a phase II study in 76 patients with advanced breast cancer.

Patients and Methods: Two cohorts of patients were recruited sequentially. The first cohort (n = 41) received a continuous dosing [CD] regimen of R115777 400 or 300 mg bid. The second cohort (n = 35) received 300 mg bid in a cyclical regimen of 21 days of treatment followed by 7 days of rest (intermittent dosing [ID]).

Results: In the CD cohort, four patients (10%) had a partial response (PR) and six patients (15%) had stable disease at ≥ 24 weeks (SD). In the ID cohort, five patients (14%) had a PR and three patients (9%) had prolonged SD. The first six patients in the CD cohort treated at 400 mg bid all developed grade 3 to 4 neutropenia, so the subsequent 35 patients were treated at 300 mg bid. The incidence of hematologic toxicity was significantly lower in the ID than in the CD (300-mg bid) cohort: grade 3 to 4 neutropenia (14% v 43%; P = .016) and grade 3 to 4 thrombocytopenia (3% v 26%; P = .013). One patient in the ID cohort developed grade 2 to 3 neurotoxicity compared with 15 patients in the CD cohort (3% v 37%; P = .0004).

Conclusion: The farnesyl transferase inhibitor R115777 has demonstrated clinical activity in patients with metastatic breast cancer, and the ID regimen has a significantly improved therapeutic index compared with the CD regimen.
Phase I Trial of Concurrent Twice-Weekly Recombinant Human Interleukin-12 Plus Low-Dose IL-2 in Patients With Melanoma or Renal Cell Carcinoma
Authors: Gollob Jared A. , Veenstra Korina G. , Parker Robert A. , Mier James W. , McDermott David F. , Clancy Daniel , Tutin Linda , Koon Henry , Atkins Michael B.
Published: June 2003

Purpose: To maintain interferon gamma (IFNγ) induction by recombinant human interleukin-12 (rhIL-12) and enhance its activity against melanoma and renal cell cancer, a regimen of twice-weekly intravenous (IV) rhIL-12 was modified to include concurrent low-dose subcutaneous (SC) IL-2 in a phase I dose escalation study.

Patients and Methods: Patients received 6-week cycles of twice-weekly IV rhIL-12 at doses of 300 to 500 ng/kg. Midway through cycle 1, low-dose SC IL-2 was added. The IL-2 was escalated from 0.5 to 6.0 MU/m2. Grade 3 elevations of hepatic ALT, AST, or alkaline phosphatase were not considered dose-limiting unless values were more than 10 times normal. During cycle 1, patients underwent immune monitoring to assess the effect of IL-2 on lymphocyte activation and cytokine production induced by rhIL-12.

Results: Twenty-eight patients were enrolled onto the study. The maximum-tolerated dose (MTD) was 500 ng/kg rhIL-12 plus 3 MU/m2IL-2. Toxicities related to the addition of IL-2 at the MTD included fever or chills, anemia, fatigue, nausea or vomiting, and orthostatic hypotension. At the MTD, IL-2 significantly augmented IFNγ and IFNγ-inducible protein-10 production by rhIL-12 and led to a three-fold expansion of natural killer cells. There was one major clinical response (partial response) as well as two pathologic responses; all occurred in melanoma patients. Stable disease for three to six cycles was only observed at or above the MTD in melanoma and renal cell cancer patients.

Conclusion: The addition of concurrent low-dose IL-2 to rhIL-12 is well tolerated, restores and maintains immune activation by rhIL-12, and has clinical activity. This regimen should be further investigated in phase II studies in untreated patients with melanoma or renal cell cancer and in other rhIL-12–responsive malignancies.
Molecular markers for identified neuroblasts in the developing brain ofDrosophila
Authors: Urbach Rolf , Technau Gerhard M.
Published: June 2003

The Drosophila brain develops from the procephalic neurogenic region of the ectoderm. About 100 neural precursor cells (neuroblasts)delaminate from this region on either side in a reproducible spatiotemporal pattern. We provide neuroblast maps from different stages of the early embryo(stages 9, 10 and 11, when the entire population of neuroblasts has formed),in which about 40 molecular markers representing the expression patterns of 34 different genes are linked to individual neuroblasts. In particular, we present a detailed description of the spatiotemporal patterns of expression in the procephalic neuroectoderm and in the neuroblast layer of the gap genes empty spiracles, hunchback, huckebein, sloppy paired 1 and tailless; the homeotic gene labial; the early eye genes dachshund, eyeless and twin of eyeless; and several other marker genes (including castor, pdm1, fasciclin 2, klumpfuss, ladybird,runt and unplugged). We show that based on the combination of genes expressed, each brain neuroblast acquires a unique identity, and that it is possible to follow the fate of individual neuroblasts through early neurogenesis. Furthermore, despite the highly derived patterns of expression in the procephalic segments, the co-expression of specific molecular markers discloses the existence of serially homologous neuroblasts in neuromeres of the ventral nerve cord and the brain. Taking into consideration that all brain neuroblasts are now assigned to particular neuromeres and individually identified by their unique gene expression, and that the genes found to be expressed are likely candidates for controlling the development of the respective neuroblasts, our data provide a basic framework for studying the mechanisms leading to pattern and cell diversity in the Drosophilabrain, and for addressing those mechanisms that make the brain different from the truncal CNS.
Acquisition of Hox codes during gastrulation and axial elongation in the mouse embryo
Authors: Forlani Sylvie , Lawson Kirstie A. , Deschamps Jacqueline
Published: June 2003

Early sequential expression of mouse Hox genes is essential for their later function. Analysis of the relationship between early Hox gene expression and the laying down of anterior to posterior structures during and after gastrulation is therefore crucial for understanding the ontogenesis of Hox-mediated axial patterning. Using explants from gastrulation stage embryos,we show that the ability to express 3′ and 5′ Hox genes develops sequentially in the primitive streak region, from posterior to anterior as the streak extends, about 12 hours earlier than overt Hox expression. The ability to express autonomously the earliest Hox gene, Hoxb1, is present in the posterior streak region at the onset of gastrulation, but not in the anterior region at this stage. However, the posterior region can induce Hoxb1 expression in these anterior region cells. We conclude that tissues are primed to express Hox genes early in gastrulation, concomitant with primitive streak formation and extension, and that Hox gene inducibility is transferred by cell to cell signalling.

Axial structures that will later express Hox genes are generated in the node region in the period that Hox expression domains arrive there and continue to spread rostrally. However, lineage analysis showed that definitive Hox codes are not fixed at the node, but must be acquired later and anterior to the node in the neurectoderm, and independently in the mesoderm. We conclude that the rostral progression of Hox gene expression must be modulated by gene regulatory influences from early on in the posterior streak, until the time cells have acquired their stable positions along the axis well anterior to the node.
Delta-Notch signaling regulates oligodendrocyte specification
Authors: Park Hae-Chul , Appel Bruce
Published: June 2003

Oligodendrocytes, the myelinating cell type of the central nervous system,arise from a ventral population of precursors that also produces motoneurons. Although the mechanisms that specify motoneuron development are well described, the mechanisms that generate oligodendrocytes from the same precursor population are largely unknown. By analysing mutant zebrafish embryos, we found that Delta-Notch signaling is required for spinal cord oligodendrocyte specification. Using a transgenic, conditional expression system, we also learned that constitutive Notch activity could promote formation of excess oligodendrocyte progenitor cells (OPCs). However, excess OPCs are induced only in ventral spinal cord at the time that OPCs normally develop. Our data provide evidence that Notch signaling maintains subsets of ventral spinal cord precursors during neuronal birth and, acting with other temporally and spatially restricted factors, specifies them for oligodendrocyte fate.
Modes of intercellular transcription factor movement in theArabidopsisapex
Authors: Wu Xuelin , Dinneny José R. , Crawford Katrina M. , Rhee Yoon , Citovsky Vitaly , Zambryski Patricia C. , Weigel Detlef
Published: June 2003

A recent and intriguing discovery in plant biology has been that some transcription factors can move between cells. In Arabidopsis thaliana, the floral identity protein LEAFY has strong non-autonomous effects when expressed in the epidermis, mediated by its movement into underlying tissue layers. By contrast, a structurally unrelated floral identity protein, APETALA1, has only limited non-autonomous effects. Using GFP fusions to monitor protein movement in the shoot apical meristem and in floral primordia of Arabidopsis, we found a strong correlation between cytoplasmic localization of proteins and their ability to move to adjacent cells. The graded distribution of several GFP fusions with their highest levels in the cells where they are produced is compatible with the notion that this movement is driven by diffusion. We also present evidence that protein movement is more restricted laterally within layers than it is from L1 into underlying layers of the Arabidopsis apex. Based on these observations, we propose that intercellular movement of transcription factors can occur in a non-targeted fashion as a result of simple diffusion. This hypothesis raises the possibility that diffusion is the default state for many macromolecules in the Arabidopsis apex, unless they are specifically retained.
Differential expression of theDrosophilaBX-C in polytene chromosomes in cells of larval fat bodies: a cytological approach to identifying in vivo targets of the homeotic Ubx, Abd-A and Abd-B proteins
Authors: Marchetti Marcella , Fanti Laura , Berloco Maria , Pimpinelli Sergio
Published: June 2003

We have analyzed the expression of homeotic Bithorax Complex proteins in the fat bodies of Drosophila larvae by staining with specific antibodies. We have found that these proteins are differentially expressed along the anteroposterior (AP) axis of the fat body, with patterns parallel to those previously characterized for the larval and adult epidermis. As fat body nuclei have polytene chromosomes, we were able to identify the BX-C locus and show that it assumes a strongly puffed conformation in cells actively expressing the genes of the BX-C. Immunostaining of these polytene chromosomes provided the resolution to cytologically map binding sites of the three proteins: Ubx, Abd-A and Abd-B. The results of this work provide a system with which to study the positioning of chromatin regulatory proteins in either a repressed and/or active BXC at the cytological level. In addition, the results of this work provide a map of homeotic target loci and thus constitute the basis for a systematic identification of genes that are direct in vivo targets of the BX-C genes.
Targeted expression ofshibirets andsemaphorin 1areveals critical periods for synapse formation in the giant fiber ofDrosophila
Authors: Murphey R. K. , Froggett Stephan J. , Caruccio Phyllis , Shan-Crofts Xiaoliang , Kitamoto Toshihiro , Godenschwege Tanja A.
Published: June 2003

In order to determine the timing of events during the assembly of a neural circuit in Drosophila we targeted expression of the temperature-sensitive shibire gene to the giant fiber system and then disrupted endocytosis at various times during development. The giant fiber retracted its axon or incipient synapses when endocytosis was blocked at critical times, and we perceived four phases to giant fiber development: an early pathfinding phase, an intermediate phase of synaptogenesis, a late stabilization process and, finally, a mature synapse. By co-expressing shibirets and semaphorin 1a we provided evidence that Semaphorin 1a was one of the proteins being regulated by endocytosis and its removal was a necessary part of the program for synaptogenesis. Temporal control of targeted expression of the semaphorin 1a gene showed that acute excess Semaphorin 1a had a permanent disruptive effect on synapse formation.
Integrins modulate Sog activity in theDrosophilawing
Authors: Araujo Helena , Negreiros Erika , Bier Ethan
Published: June 2003

Morphogenesis of the Drosophila wing depends on a series of cell-cell and cell-extracellular matrix interactions. During pupal wing development, two secreted proteins, encoded by the short gastrulation(sog) and decapentaplegic (dpp) genes, vie to position wing veins in the center of broad provein territories. Expression of the Bmp4 homolog dpp in vein cells is counteracted by expression of the Bmp antagonist sog in intervein cells, which results in the formation of straight veins of precise width. We screened for genetic interactions between sog and genes encoding a variety of extracellular components and uncovered interactions between sog and myospheroid (mys), multiple edematous wing(mew) and scab (scb), which encode βPS,αPS1 and αPS3 integrin subunits, respectively. Clonal analysis reveals that integrin mutations affect the trajectory of veins inside the provein domain and/or their width and that misexpression of sog can alter the behavior of cells in such clones. In addition, we show that a low molecular weight form of Sog protein binds to αPS1βPS. We find that Sog can diffuse from its intervein site of production into adjacent provein domains, but only on the dorsal surface of the wing, where Sog interacts functionally with integrins. Finally, we show that Sog diffusion into provein regions and the reticular pattern of extracellular Sog distribution in wild-type wings requires mys and mew function. We propose that integrins act by binding and possibly regulating the activity/availability of different forms of Sog during pupal development through an adhesion independent mechanism.
Whose Responsibility Is It to Define Exceptions in Abortion Bans?
Authors: Shachar Carmel , Baruch Susannah , King Louise P.
Published: January 2024

This Viewpoint evaluates Texas’ proposals to define the scope of the life exception for the state’s abortion ban and argues that these approaches do not allow physicians to follow the national standards of care, avoid criminal liability, or have sufficient notice of what the law permits.
Diffusely Enhancing Lesions on MRI in DPPX Antibody-Associated Encephalitis
Authors: Liu Mao , Qin Chuan , Tian Dai-Shi
Published: January 2024

This case report describes a diagnosis of dipeptidyl-peptidaselike protein-6 antibody-associated encephalitis in a woman aged 51 years who presented with progressive gait instability, memory impairment, and weight loss.