bluuebunny/crossref_metadata_2025_split huggingface dataset:
PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism
Authors: Walter Roland B. , Pirga Jason L. , Cronk Michelle R. , Mayer Sasha , Appelbaum Frederick R. , Banker Deborah E. 
Published: July 2005

AbstractThe peripheral benzodiazepine receptor (pBR) ligand, PK11195, promotes mitochondrial apoptosis and blocks P-glycoprotein (Pgp)-mediated drug efflux to chemosensitize cancer cells at least as well or better than the Pgp modulator, cyclosporine A (CSA). We now show that PK11195 broadly inhibits adenosine triphosphate (ATP)-binding cassette (ABC) transporters in hematologic cancer cell lines and primary leukemia-cell samples, including multidrug resistance protein (MRP), breast cancer resistance protein (BCRP), and/or Pgp. Ectopic expression models confirmed that pBR can directly mediate chemosensitizing by PK11195, presumably via mitochondrial activities, but showed that pBR expression is unnecessary to PK11195-mediated efflux inhibition. PK11195 binds plasma-membrane sites in Pgp-expressing cells, stimulates Pgp-associated adenosine triphosphatase (ATPase) activity, and causes conformational changes in Pgp, suggesting that PK11195 modulates Pgp-mediated efflux by direct transporter interaction(s). PK11195 and CSA bind noncompetitively in Pgp-expressing cells, indicating that PK11195 interacts with Pgp at sites that are distinct from CSA-binding sites. Importantly, PK11195 concentrations that were effective in these in vitro assays can be safely achieved in patients. Because PK11195 promotes chemotherapy-induced apoptosis by a pBR-dependent mitochondrial mechanism and broadly blocks drug efflux by an apparently pBR-independent, ABC transporter-dependent mechanism, PK11195 may be a useful clinical chemosensitizer in cancer patients.
Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma
Authors: Kundu Mondira , Compton Sheila , Garrett-Beal Lisa , Stacy Terryl , Starost Matthew F. , Eckhaus Michael , Speck Nancy A. , Liu P. Paul 
Published: July 2005

AbstractChromosomal rearrangements affecting RUNX1 and CBFB are common in acute leukemias. These mutations result in the expression of fusion proteins that act dominant-negatively to suppress the normal function of the Runt-related transcription factor 1 (RUNX)/core binding factor β (CBFβ) complexes. In addition, loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) have been identified in sporadic cases of acute myeloid leukemia (AML) and in association with the familial platelet disorder with propensity to develop AML (FPD/AML). In order to examine the hypothesis that decreased gene dosage of RUNX1 may be a critical event in the development of leukemia, we treated chimeric mice generated from Runx1lacZ/lacZ embryonic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an increased incidence of T-lymphoblastic lymphoma in Runx1lacZ/lacZ compared with wild-type chimeras and confirmed that the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can indeed predispose mice to hematopoietic malignancies.
Analysis of the function of E. coli 23S rRNA helix-loop 69 by mutagenesis
Authors: Liiv Aivar , Karitkina Diana , Maiväli Ülo , Remme Jaanus 
Published: July 2005

Abstract

Background
The ribosome is a two-subunit enzyme known to exhibit structural dynamism during protein synthesis. The intersubunit bridges have been proposed to play important roles in decoding, translocation, and the peptidyl transferase reaction; yet the physical nature of their contributions is ill understood. An intriguing intersubunit bridge, B2a, which contains 23S rRNA helix 69 as a major component, has been implicated by proximity in a number of catalytically important regions. In addition to contacting the small ribosomal subunit, helix 69 contacts both the A and P site tRNAs and several translation factors.

Results
We scanned the loop of helix 69 by mutagenesis and analyzed the mutant ribosomes using a plasmid-borne IPTG-inducible expression system. We assayed the effects of 23S rRNA mutations on cell growth, contribution of mutant ribosomes to cellular polysome pools and the ability of mutant ribosomes to function in cell-free translation. Mutations A1912G, and A1919G have very strong growth phenotypes, are inactive during in vitro protein synthesis, and under-represented in the polysomes. Mutation Ψ1917C has a very strong growth phenotype and leads to a general depletion of the cellular polysome pool. Mutation A1916G, having a modest growth phenotype, is apparently defective in the assembly of the 70S ribosome.

Conclusion
Mutations A1912G, A1919G, and Ψ1917C of 23S rRNA strongly inhibit translation. Mutation A1916G causes a defect in the 50S subunit or 70S formation. Mutations Ψ1911C, A1913G, C1914A, Ψ1915C, and A1918G lack clear phenotypes.
Welcome to Journal of Ethnobiology and Ethnomedicine
Authors: Pieroni Andrea , Price Lisa Leimar , Vandebroek Ina 
Published: July 2005

Abstract
Ethnobiology is a multidisciplinary field of study that draws on approaches and methods from both the social and biological sciences. Ethnobiology aims at investigating culturally based biological and environmental knowledge, cultural perception and cognition of the natural world, and associated behaviours and practices. Ethnomedicine is concerned with the cultural interpretations of health, disease and illness and also addresses the health care seeking process and healing practices. Research interest and activities in the areas of ethnobiology and ethnomedicine have increased tremendously in the last decade. Since the inception of the disciplines, scientific research in ethnobiology and ethnomedicine has made important contributions to understanding traditional subsistence and medical knowledge and practice. The Journal of Ethnobiology and Ethnomedicine (JEE) invites manuscripts and reviews based on original interdisciplinary research from around the world on the inextricable relationships between human cultures and nature, on Traditional Environmental Knowledge (TEK), folk and traditional medical knowledge, as well as on the relevance of the above for Primary Health Care (PHC) policies in developing countries.
Common mental disorders in a young urban population in Colombia
Authors: Harpham Trudy , Snoxell Simon , Grant Emma , Rodriguez Carlos 
Published: July 2005

BackgroundThere are few studies of mental ill health among young people in developing countries.AimsTo measure the prevalence of common mental disorders among low-income young people in the city of Cali, Colombia and to examine associations with violence and social capital.MethodThe Self-Reporting Questionnaire was administered to 1057 young people aged 15–25 years. Social capital, violence, alcoholism and socio-demographic variables were also measured.ResultsWe found 255 young people (24%) with common mental disorders. Being a woman, having limited education and experiencing high levels of violence were the main risk factors for common mental disorders. Social capital did not emerge as a risk factor.ConclusionsA large burden of mental ill health among young people was found; this requires urgent interventions and more research on the mechanisms which link mental health and violence.
Introduction to ‘Early psychosis: abridge to the future’
Authors: Mcgorry Patrick , Nordentoft Merete , Simonsen Erik 
Published: July 2005

SummaryEarly intervention in psychiatry has taken a long time to emerge as a key strategy to reduce morbidity and mortality. In other fields of medicine it has received consistent support and great efforts are expended to educate the public about the value of early diagnosis and the benefits of timely intervention. There is finally substantial momentum behind similar endeavours in psychotic disorders, which, now they have reached ‘proof of concept’ stage, could begin to be extended across the spectrum of serious mental disorders. There is also ambivalence and resistance to this evidence-based reform which warrants careful analysis. The Third International Early Psychosis Conference proved to be a watershed and was the largest and most vibrant meeting to that point. This preface aims to set the scene for a selection of contributions, derived from the array of new evidence reported in Copenhagen, and recently fully updated.
Early detection and intervention in psychosis: an ethical paradigm shift
Authors: Mcglashan Thomas H. 
Published: July 2005

SummaryThis paper will first posit the rationale for intervention before onset, then outline the current usual practice of treating schizophrenia and the determinants ofthat practice. Recent developments that permit or demand a change in this practice will then be elaborated. The article concludes with an elaboration of the currently known risks and benefits of early intervention research. The ethics of early intervention are undergoing a paradigm shift, a shift that supports early intervention research as being necessary to bring empirical balance to territory that is currently overpopulated with zealous opinions.Delcaration of interestNone.
Duration of untreated psychosis and its relationship to clinical outcome
Authors: Norman Ross M. G. , Lewis Shôn W , Marshall Max 
Published: July 2005

BackgroundA major reason for interest in early intervention for psychotic disorders is the hypothesised relationship between longer duration of untreated psychosis (DUP) and poorer outcome of treatment.AimsTo critically examine the evidence concerning DUP being related to treatment outcome and possible mediators of any such relationship.MethodA systematic review of studies in which DUP is assessed and its relationship to treatment outcome is examined. In addition, studies relevant to possible neurotoxic effects of DUP were reviewed.ResultsThe research is entirely of a correlational nature and, therefore, firm conclusions regarding causation are not possible. There is, however, substantial evidence of DUP being an independent predictor of treatment outcome, particularly remission of positive symptoms, over the first year or so of treatment. Findings regarding the possible neurotoxic effects of DUP are inconsistent.ConclusionsThere continues to be evidence consistent with DUP influencing aspects of treatment outcome. Non-correlational studies, such as quasi-experimental designs, could provide stronger evidence regarding causality.
Neurobiology of early psychosis
Authors: Keshavan Matcheri S. , Berger Gregor , Zipursky Robert B. , Pantelis Christos , Wood Stephen J. , Pantelis Christos 
Published: July 2005

BackgroundNeurobiological studies of the early course of psychoses, such as schizophrenia, allow investigation of pathophysiology without the confounds of illness chronicity and treatment.AimsTo review the recent literature on the biology of the early course of psychoses.MethodWe carried out a critical appraisal of the recent findings in the neurobiology of early psychoses, using structural, functional and neurochemical imaging techniques.ResultsBrain structural alterations are present early in the illness and may predate symptom onset. Some changes, notably those in frontal and temporal lobes, can progress during the early phases of the illness. Functional and neurochemical brain abnormalities can also be seen in the premorbid and the early phases of the illness. Some, although not all, changes can be trait-like whereas some others might progress during the early years.ConclusionsA better understanding of such changes, especially during the critical periods of the prodrome, around the transition to the psychotic phase and during the early phases of the illness is crucial for continued research into preventive intervention strategies.
Contractile activity of the pectoralis in the zebra finch according to mode and velocity of flap-bounding flight
Authors: Tobalske Bret W. , Puccinelli Lisa A. , Sheridan David C. 
Published: July 2005

SUMMARYWe studied flying zebra finch (Taeniopygia guttata, N=12), to provide a new test of a long-standing `fixed-gear'hypothesis that flap-bounding birds use only intermittent non-flapping phases,instead of variation in muscle activity, to vary mechanical power output in flight. Using sonomicrometry and electromyography, we measured in vivo fascicle length and neuromuscular recruitment in the pectoralis as the birds flew in different flight modes (level, ascending, descending; mean velocity 1.6±0.3 m s–1) and across velocities in a new, variable-speed wind tunnel (0–12 m s–1). Synchronized high-speed digital video (250 Hz) provided a record of wing kinematics. Flight mode had a significant effect upon pectoralis strain,strain rate, fractional shortening and the relative timing of muscle activity(onset, offset and duration). Among flight velocities, we observed significant variation in pectoralis strain, fractional lengthening and shortening, strain rate, relative electromyographic (EMG) amplitude, and EMG duration and offset. In particular, variation in strain rate and relative EMG amplitude indicates that the fixed-gear hypothesis should be rejected. Instead, it appears that zebra finch vary work and power output within wingbeats by modulating muscle contractile behavior and between wingbeats using intermittent bounds. Muscle activity patterns and wing kinematics were similar between free flight and wind tunnel flight at similar speeds. Comparing flights with and without surgically implanted transducers and electrodes, zebra finch exhibited a reduction in maximum velocity (from 14 to 12 m s–1) and a significant increase in wingbeat frequency and percent time flapping. This identifies a potential limitation of in vivo flight measurements, and similar studies of bird flight should, therefore, include measurements of the extent to which flight performance is compromised by experimental protocol.
Ontogenetic effects on aerobic and anaerobic metabolism during jumping in the American locust,Schistocerca americana
Authors: Kirkton Scott D. , Niska Jared A. , Harrison Jon F. 
Published: July 2005

SUMMARYDeveloping vertebrates increase both their locomotory power output and endurance due to ontogenetic improvements in anaerobic and aerobic metabolic capacities. Do similar patterns hold for insect locomotion, or do longer tracheal lengths create problems for oxygen delivery in older animals? We forced developing American locust grasshoppers (Schistocerca americana) to jump repeatedly and examined the effect of development on power output, endurance, lactate concentration, oxygen consumption and the oxygen sensitivity of jump performance. As previously shown, power outputs,relative leg lengths and leg cuticular content increased with age. A key finding of this study is that both lactate concentration and aerobic metabolic rate of the jumping muscle increase with age, explaining how the increased leg cuticular stiffness can result in increased power output. After two minutes of jumping, grasshoppers rely completely on aerobic ATP production. The rise in mass-specific, active aerobic metabolic rates with age indicates that problems with longer tracheae can be overcome; however, the reduced endurance, higher lactate concentrations and increased oxygen sensitivity of locomotory performance in older animals indicate that larger/older grasshoppers have smaller safety margins for oxygen delivery during hopping.
The Dirty Dozen: 12 Myths That Undermine Tobacco Control
Authors: Frieden Thomas R. , Blakeman Drew E. 
Published: July 2005

Cigarette smoking is the leading cause of preventable death in the United States. The health risks of smoking are well documented, as is the effectiveness of clinical and public health interventions to prevent and reduce smoking. However, many myths about smoking either encourage people to begin or continue smoking or deter them from quitting. Some myths stem from a misapplied understanding of what might seem to be common sense; others are deliberately promulgated by the tobacco industry to induce people—especially children—to start smoking and to keep them smoking as adults. These myths undermine tobacco control. However, comprehensive tobacco control programs that include anti-smoking public education campaigns can effectively counter these myths and prevent illness and premature death.
Patents
Authors: Lang Christian 
Published: July 2005

Abstract
This article provides an overview on patents and protective rights in general. First of all information is given which protective rights exist and what can be protected by these rights. Afterwards, general principles of patent law are presented which are common to many national patent laws and international treaties regarding industrial property throughout the world. A main focus of this presentation is directed to the description of the proceedings according to the Patent Cooperation Treaty (PCT) and the European Patent Convention. Furthermore, the particularities of US patent law are considered.

The article contains sections titled:

1.

Introduction

2.

Industrial Property and Types of Protective Rights

2.1.

Technical Protective Rights (Patents, Utility Models)

2.2.

Trademarks

2.3.

Design Patents/Industrial Designs

2.4.

Copyright

2.5.

Others

3.

Basic Principles of Patents

3.1.

Invention

3.2.

Exclusive Privilege

3.3.

Principle of Territoriality

3.4.

Period of Protection

3.5.

Ways of Establishing Patents

3.6.

Priority

3.7.

Novelty

3.8.

Inventive Step/Nonobviousness

3.9.

Industrial Application

4.

System of International Treaties

4.1.

Paris Convention

4.2.

Patent Cooperation Treaty

4.3.

Regional Treaties

5.

Patent Cooperation Treaty (PCT)

5.1.

Application

5.2.

Search

5.3.

Preliminary Examination

5.4.

Entry into National/Regional Phase

6.

European Patent Convention

6.1.

Member States

6.2.

Application Proceedings

6.2.1.

Application

6.2.2.

Examination Procedure

6.3.

Opposition Proceedings

6.4.

Appeal

7.

U.S. Patents

8.

Other National Law
Astronomical Telescopes and Instrumentation
Authors: Fried Josef W. 
Published: July 2005

Abstract
Optical and mechanical designs of ground‐based astronomical telescopes for the visible region are reviewed, including special‐purpose telescopes and planned new designs for very large telescopes. The efforts to increase the angular resolution by adaptive optics are described. An overview is given of the instrumentation that is attached to telescopes to analyze and register the light collected by the telescope.
Biomedical Imaging Techniques
Authors: Hendee William R. 
Published: July 2005

AbstractBiomedical images are used extensively for noninvasive exploration of the internal anatomy, physiology, and metabolism of patients suffering from virtually every disease and injury known to humankind. These images are a prototypical example of “high‐tech” medicine and are produced in many different ways, from receipt of X rays transmitted through the patient to detection of radio‐frequency signals emitted from tissues subjected to intense magnetic fields. In the past three decades, major advances in medical imaging have occurred, including X‐ray and emission‐computed tomography, real‐time, gray‐scale and Doppler ultrasound imaging, computer and digital projection radiography, and magnetic resonance imaging. Several additional imaging techniques are under exploration, including laser optical imaging, electrical impedance tomography, infrared and microwave thermography, acoustothermometry, and electrical and magnetic source imaging. Whether these or a completely new imaging technique may emerge as a significant imaging modality remains to be seen. In the meantime, additional applications of existing medical imaging methods continue to be identified, such as the use of functional magnetic resonance and emission‐computed tomography for planning and monitoring radiation treatments for cancer.
Interferometry
Authors: Hariharan Parameswaran , Creath Katherine 
Published: July 2005

Abstract
This article reviews the field of interferometry. It begins by outlining the fundamentals of two‐beam and multiple‐beam interference. The rest of the article discusses the applications of interferometry for measurement of length, optical testing, fringe analysis, interference microscopy, interferometric sensors, interference spectroscopy, nonlinear interferometers, interferometric imaging, space‐time and gravitation, holographic interferometry, Moiré techniques, and speckle interferometry. Each section provides a referenced (and cross‐referenced) overview of the application area.
Microscopy
Authors: Hellmuth Thomas 
Published: July 2005

AbstractPrinciples, methods, and applications of light microscopy, electron microscopy, and scanning probe microscopy are described and complemented by related techniques such as ultrasound microscopy, field‐emission microscopy and X‐ray microscopy. Advanced methods such as Raman microscopy, low‐energy electron microscopy, and scanning near‐field microscopy representing new trends in the field of microscopy are discussed.
Optical Materials
Authors: Jellison Gerald E. 
Published: July 2005

Abstract
Transparent optical materials are used in a variety of applications ranging from the very common, such as corrective lenses, to the very sophisticated, such as fiber‐optic communications. As common as these applications are, optical materials possess many interesting and complicating properties, which are often ignored. For example, all optical materials absorb light in some spectral regions, and all materials experience dispersion, where the refractive index is a function of the wavelength of light. In this chapter, the basic physics of light interaction with optical materials is presented, primarily to explain many of these commonly observed phenomena. The emphasis of the chapter is on materials that are transparent in the region from the ultraviolet (down to ∼120 nm) to the mid‐infrared (up to ∼40 microns). Perturbations of the basic optical properties of materials, such as those due to external strain and electric fields, will also be discussed. The properties of several specific optical materials will be discussed with the intent of demonstrating the basic physics and not to present a comprehensive listing of optical data. Thin films (that is, films with thicknesses on the order of the wavelength of light) are also discussed with the intent of understanding the physics of these materials and how they interact with light to produce the desired affects, such as reducing or enhancing the amount of light transmitted through or reflected from an optical device.
Atmospheric Optics
Authors: Bohren Craig F. 
Published: July 2005

AbstractColors of the sky and colored displays in the sky are mostly a consequence of selective scattering by molecules or particles, absorption usually being irrelevant. Molecular scattering selective by wavelength—incident sunlight of some wavelengths being scattered more than others—but the same in any direction at all wavelengths gives rise to the blue of the sky and the red of sunsets and sunrises. Scattering by particles selective by direction—different in different directions at a given wavelength—gives rise to rainbows, coronas, iridescent clouds, the glory, sun dogs, halos, and other ice‐crystal displays. The size distribution of these particles and their shapes determine what is observed, water droplets and ice crystals, for example, resulting in distinct displays.To understand the variation and color and brightness of the sky as well as the brightness of clouds requires coming to grips with multiple scattering: scatterers in an ensemble are illuminated by incident sunlight and by the scattered light from each other. The optical properties of an ensemble are not necessarily those of its individual members.Mirages are a consequence of the spatial variation of coherent scattering (refraction) by air molecules, whereas the green flash owes its existence to both coherent scattering by molecules and incoherent scattering by molecules and particles.