bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Aspects of the Lymphocyte Traffic in Rat
Submandibular Lymph Node
Authors: Okada Shigenori , Albrecht Ralph M. , Aharinejad Seyedhossein , Schraufnagel Dean E.
Published: November 2002

Modulation of lymphocyte flow in the lymphatic compartment
of the lymph node may serve, in part, to promote lymphocyte
sensitization during an antigenic challenge. This study was
undertaken to show where this might occur by examining the
structural relationships of the intranodal lymphatic pathways,
blood vessels, and connective tissue support with respect to
lymphocyte and lymph flow. Differently stained plastic resins
were injected into the blood vessels and lymphatics of the
submandibular lymph node and visualized with a confocal laser
scanning microscope. The specimens were corroded to study the
three-dimensional cast structures by scanning electron microscopy.
Alkali digestion was also used to prepare the reticular fiber
network in the lymph node for scanning electron microscopic
examination. At the hilus of the node, two to three arteries
gave off arterioles running in medullary cords towards the cortex.
The medullary cords, the periphery of the deep cortex, and the
perifollicular zones had dense capillary networks. In contrast,
the center of the follicle and the center of the deep cortex
were less highly vascularized. High-endothelial venules were
restricted to the perifollicular zone and the periphery of the
deep cortex. At the cortico-medullary boundary, they abruptly
transformed into medullary venules with a normal endothelium.
The marginal sinus of the lymph node was crossed by thick reticular
fibers that arose from the inner sheets of the capsule. The
lymph pathway went through the marginal sinus, into the trabecular
sinus, to the cortical perifollicular sinus, the dense lymphatic
sinus around the deep cortex, and finally into the medullary
sinus. At present, the exact functional significance of the
complex lymph node lymphatic architecture is not clear. However,
the highly organized structural organization may play a significant
role in regulating and directing lymphocyte flow to facilitate
antigen presentation.
Synthesis and Microstructural Analysis of
Si3N4 Nanorods
Authors: Gao Y.H. , Bando Y. , Kurashima K. , Sato T.
Published: November 2002

α-Si3N4 nanorods with 20–80 nm
width were synthesized by carbothermal reduction of SiO with
amorphous activated carbon (AAC) as a reductant. Microstructural
characterization of the synthesized nanorods was carried out by high
resolution transmission electron microscopy (HRTEM) and energy dispersive
X-ray analysis. Many Si3N4 nanorods were found
to be twisted. Each twisted nanorod contained several straight
Si3N4 parts. The straight parts had the rod
axes orientated along the 〈1010〉 direction, which
is the closest packing direction of α-Si3N4.
There were two kinds of joints between the two adjacent straight
Si3N4 parts. Formation mechanism of the
Si3N4 nanorods is discussed.
Active Alu Element “A-Tails”: Size Does Matter
Authors: Roy-Engel Astrid M. , Salem Abdel-Halim , Oyeniran Oluwatosin O. , Deininger Lisa , Hedges Dale J. , Kilroy Gail E. , Batzer Mark A. , Deininger Prescott L.
Published: November 2002

Long and short interspersed elements (LINEs and SINEs) are retroelements that make up almost half of the human genome. L1 and Alu represent the most prolific human LINE and SINE families, respectively. Only a few Alu elements are able to retropose, and the factors determining their retroposition capacity are poorly understood. The data presented in this paper indicate that the length of Alu “A-tails” is one of the principal factors in determining the retropositional capability of an Alu element. The A stretches of the Alu subfamilies analyzed, both old (Alu S and J) and young (Ya5), had a Poisson distribution of A-tail lengths with a mean size of 21 and 26, respectively. In contrast, the A-tails of very recent Alu insertions (disease causing) were all between 40 and 97 bp in length. The L1 elements analyzed displayed a similar tendency, in which the “disease”-associated elements have much longer A-tails (mean of 77) than do the elements even from the young Ta subfamily (mean of 41). Analysis of the draft sequence of the human genome showed that only about 1000 of the over one million Alu elements have tails of 40 or more adenosine residues in length. The presence of these long A stretches shows a strong bias toward the actively amplifying subfamilies, consistent with their playing a major role in the amplification process. Evaluation of the 19 Alu elements retrieved from the draft sequence of the human genome that are identical to the Alu Ya5a2 insert in the NF1 gene showed that only five have tails with 40 or more adenosine residues. Sequence analysis of the loci with the Alu elements containing the longest A-tails (7 of the 19) from the genomes of the NF1 patient and the father revealed that there are at least two loci with A-tails long enough to serve as source elements within our model. Analysis of the A-tail lengths of 12 Ya5a2 elements in diverse human population groups showed substantial variability in both the Alu A-tail length and sequence homogeneity. On the basis of these observations, a model is presented for the role of A-tail length in determining which Alu elements are active.

[The sequence data from this study have been submitted to GenBank under accession nos.AF504933–AF505511.]
A simple simulator of protein crystallization
Authors: Gopalakrishnan Vanathi , Buchanan B. G. , Rosenberg John
Published: November 2002

The development of an approximate physical model that can be used for simulating different types of protein crystallization behavior in response to varying physico-chemical environments is presented. The model has face validity in that it is possible to simulate different types of protein response behavior, for example, proteins that crystallize under a broad range of conditions, a narrow range of conditions, or proteins that take a very long time to nucleate and grow. A prototype parallel experiment planning (PEP) system has been developed, which can act as a tutor for novice crystallographers by enabling them to try different strategies or experimental protocols for crystallizing `hypothetical' proteins under different resource constraints. The system uses the model developed in this paper as an evaluation function that returns different observation values for an experiment over time.
Crystallization of protein–protein complexes
Authors: Radaev Sergei , Sun Peter D.
Published: November 2002

Crystallizing protein–protein complexes remains a rate-limiting step in their structure characterization. Crystallization conditions for the known protein–protein complexes have been surveyed in both the Protein Data Bank and the BMCD database. Compared with non-complexed proteins, crystallization conditions for protein–protein complexes are less diverse and heavily favor (71%versus27%) polyethylene glycols (PEG) rather than ammonium sulfate or other high-salt crystallization conditions. The results suggest that the stability of protein complexes limits their available crystallization configuration space. Based on the survey, a set of sparse-matrix screen conditions was designed.
Surface-relaxation contributions to axial screw dislocation contrast in synchrotron white-beam X-ray topographs of SiC
Authors: Vetter W. M. , Dudley M.
Published: November 2002

Micropipe images appeared in synchrotron white-beam X-ray topographs of thin basal-cut SiC wafers taken using prismatic reflections whereg · b= 0. They consisted of white ovals inclined along the direction of the topographs'gvector that were terminated with dark spikes at either end. The thin wafers tended to curl; the appearance of a defect's image varied depending on the sign of the curvature relative to the side serving as the diffracted beam's exit surface. The micropipe images were computer simulated using the ray-tracing method. The calculation assumed that they arose from the surface-relaxation strain component of a closed-core screw dislocation perpendicular to the surface of a thin foil. The qualitative features of the micropipe images were reproduced in their simulations, but the magnitude of the lattice misorientations predicted by the model was not large enough to account for the size of the experimentally observed dislocation images.
African American leadership groups: smoking with the enemy: Table 1
Authors: Yerger V B , Malone R E
Published: November 2002

Background:Among all racial and ethnic groups in the USA, African Americans bear the greatest burden from tobacco related disease. The tobacco industry has been highly influential in the African American community for decades, providing funding and other resources to community leaders and emphasising publicly its support for civil rights causes and groups, while ignoring the negative health effects of its products on those it claims to support. However, the industry’s private business reasons for providing such support were unknown.

Objective:To understand how and for what purposes the tobacco industry sought to establish and maintain relationships with African American leaders.

Methods:Review and analysis of over 700 previously secret internal tobacco industry documents available on the internet.

Results:The tobacco industry established relationships with virtually every African American leadership organisation and built longstanding social connections with the community, for three specific business reasons: to increase African American tobacco use, to use African Americans as a frontline force to defend industry policy positions, and to defuse tobacco control efforts.

Conclusion:As the tobacco industry expands its global reach, public health advocates should anticipate similar industry efforts to exploit the vulnerabilities of marginalised groups. The apparent generosity, inclusion, and friendship proffered by the industry extract a price from groups in the health of their members. Helping groups anticipate such efforts, confront industry co-optation, and understand the hidden costs of accepting tobacco industry largesse should be part of worldwide tobacco control efforts.
Tobacco spending and children in low income households
Authors: Thomson G W , Wilson N A , O’Dea D , Reid P J , Howden-Chapman P
Published: November 2002

Objective:To examine the role of tobacco use in creating financial hardship for New Zealand (NZ) low income households with children.

Data:The 1996 NZ census (smoking prevalence by household types), Statistics NZ (household spending surveys 1988-98), and NZ Customs (tobacco released from bond 1988-98).

Main outcome measures:Proportion of children in households with smokers and ≤$NZ15 000 gross income per adult. Proportion of spending on tobacco of second lowest equivalised household disposable income decile and of solo parent households.

Results:In ≤$NZ15 000 gross income per adult households with both children and smokers, there were over 90 000 children, or 11% of the total population aged less than 15 years. Enabling second lowest income decile households with smokers to be smoker-free would on average allow an estimated 14% of the non-housing budgets of those households to be reallocated.

Conclusions:The children in low income households with smokers need to be protected from the financial hardship caused by tobacco use. This protection could take the form of more comprehensive government support for such households and stronger tobacco control programmes. A reliance on tobacco price policy alone to deter smokers is likely to have mixed outcomes—for example, increased hardship among some of these households. The challenge for tobacco control is to move from a sole focus on “doing good” towards incorporating the principle of “doing no harm”.
Areas beneath the relative operating characteristics (ROC) and relative operating levels (ROL) curves: Statistical significance and interpretation
Authors: Mason S. J. , Graham N. E.
Published: November 2002

The areas beneath the relative (or receiver) operating characteristics (ROC) and relative operating levels (ROL) curves can be used as summary measures of forecast quality, but statistical significance tests for these areas are conducted infrequently in the atmospheric sciences. A development of signal‐detection theory, the ROC curve has been widely applied in the medical and psychology fields where significance tests and relationships to other common statistical methods have been established and described. This valuable literature appears to be largely unknown to the atmospheric sciences where applications of ROC and related techniques are becoming more common. This paper presents a survey of that literature with a focus on the interpretation of the ROC area in the field of forecast verification. We extend these foundations to demonstrate that similar principles can be applied to the interpretation and significance testing of the ROL area. It is shown that the ROC area is equivalent to the Mann–Whitney U‐statistic testing the significance of forecast event probabilities for cases where events actually occurred with those where events did not occur. A similar derivation shows that the ROL area is equivalent to the Mann–Whitney U‐statistic testing the magnitude of events with respect to whether or not an event has been forecast. Because the Mann–Whitney U‐statistic follows a known probability distribution, under certain assumptions it can be used to define the statistical significance of ROC and ROL areas and for comparing the areas of competing forecasts. For large samples the significance of either measure can be accurately assessed using a normal‐distribution approximation. Copyright © 2002 Royal Meteorological Society
EMS models for business strategy development
Authors: Tinsley Stephen
Published: November 2002

This research investigation identifies the organizational barriers that can occur within large organizations to impede the introduction and development of environmental management systems (EMSs). The findings from the six case study investigations into multinational electronic and telecommunications organizations enabled the construction of four categorical models: devoid, isolated, devolved and integrated. They provide a profile of the way organizations use their EMSs and detail the types of organizational barrier that are likely to occur in each case.

The models are designed to offer insight into the profile of the organization, the type of EMS being used and the operational advantages and disadvantages of using each model. They offer managers additional decision‐making tools with which to assess the EMS profile of their own organization and those of competitor organizations and to assess the effectiveness of an organization's EMS in weak and strong economic conditions. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment
Effects of maternal style on infant behavior in Japanese macaques (Macaca fuscata)
Authors: Bardi Massimo , Huffman Michael A.
Published: November 2002

We assessed the association of maternal style and infant behavior of group‐living Japanese macaques during the first year of infant development. We tested the hypothesis that different mothering styles were correlated with the behavioral repertoire of infants at three different developmental stages. We expected that infants of rejecting mothers would show a higher level of enterprise and that infants of protective mothers would be less interested in the external environment. We found evidence that maternal style affects infant behavior during the early developmental phase, but this influence becomes smaller as the infant grows older and approaches complete independence. Maternal protectiveness appears to have long‐lasting effects on infant exploration as infants of protective mothers tended to be less attracted by the external environment. On the other hand, mater‐ nal rejection appears to have long‐lasting effects on infant interaction with other group members as more rejected infants tended to initiate a significantly higher number of contacts with other juveniles and adults. These results suggest that both maternal rejection and maternal protectiveness play an important role in the independence of the offspring, in opposite directions. That is, rejection promotes independence whereas protectiveness delays it. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 364–372, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10065
The content of Third World tourism marketing: a 4A approach
Authors: Echtner Charlotte M.
Published: November 2002

Tourism to the Third World continues to grow and, correspondingly, the promotion of these regions is increasingly popular and important. Although some concerns have been voiced about the images contained in Third World tourism marketing, there has been no extensive examination of its content to date. Accordingly, in this study, the verbal and visual components of 115 brochures for 12 Third World countries are analysed. To facilitate a detailed content analysis of these brochures, a ‘4A’ approach is introduced, focusing on attractions (natural and man‐made), actors (hosts and tourists), actions and atmosphere. This comprehensive inventory reveals that Third World countries are clustered into three groups, namely Oriental, sea–sand and frontier. It is shown that by emphasising and stereotyping certain attractions, actors, actions and atmospheres, certain overarching tourism myths are created around Third World destinations. Copyright © 2002 John Wiley & Sons, Ltd.
Ultrastructural analysis of bone tissue irradiated by Er:YAG Laser
Authors: Sasaki Katia M. , Aoki Akira , Ichinose Shizuko , Ishikawa Isao
Published: November 2002

Background and Objectives

The use of erbium:yttrium aluminum garnet (Er:YAG) laser has been suggested for bone ablation, however, little is known about the nature of the tissue after irradiation. This study was aimed to analyze the ultrastructure of bone tissue treated with Er:YAG laser, as compared to those treated with CO2 laser and bur drilling.

Study Design/Materials and Methods

Parietal bones of Wistar rats were treated and analyzed by light microscopy, transmission electron microscopy (TEM), electron diffraction analysis and energy dispersive X‐ray spectroscopy (SEM–EDX).

Results

This study demonstrated that Er:YAG laser irradiation resulted in a very thin changed layer of ∼30 μm thickness, which consisted of two distinct sub‐layers: a superficial, greatly altered layer and a deep, less affected layer.

Conclusions

The major changes found on bone surface after Er:YAG laser irradiation consisted of micro‐cracking, disorganization, and slight recrystallization of the original apatites and reduction of surrounding organic matrix. Lasers Surg. Med. 31:322–332, 2002. © 2002 Wiley‐Liss, Inc.
In situ light dosimetry during photodynamic therapy of Barrett's esophagus with 5‐aminolevulinic acid
Authors: van Veen Robert L.P. , Aalders Maurice C.G. , Pasma Kasper L. , Siersema Peter D. , Haringsma Jelle , van de Vrie Wim , Gabeler Edward E.E. , Robinson Dominic J. , Sterenborg Henricus J.C.M.
Published: November 2002

Background and Objectives

Previous studies with PhotoDynamic Therapy (PDT) in bladder and bronchi have shown that due to scattering and reflection, the actually delivered fluence rate on the surface in a hollow organ can be significantly higher than expected. In this pilot study, we investigated the differences between the primary calculated and the actual measured fluence rate during PDT of Barrett's Esophagus (BE) using 23 independent clinical measurements in 15 patients.

Study Design/Materials and Methods

A KTP‐dye module laser at 630 nm was used as light source. Light delivery was performed using a cylindrical light diffuser inserted in the center of an inflatable transparent balloon with a length corresponding to the length of the Barrett's epithelium. The total light output power of the cylindrical diffuser was calibrated using an integrating sphere to deliver a primary fluence rate of 100 mW cm−2. Two fiber‐optic pseudo sphere isotropic detectors were placed on the balloon and were used to measure fluence rate at the surface of the esophageal wall during PDT.

Results and Conclusions

The actual fluence rate measured was 1.5–3.9 times higher than the primary fluence rate for 630 nm. In general, the fluence rate amplification factor decreased with increasing redness of the tissue and was less for shorter diffusers. Fluence rate variations in time were observed which coincided with patients coughing, movement, and esophageal spasms. These factors combined with inter patient variability of the fluence rate measured appears to justify the routine application of this technique in PDT of BE. Lasers Surg. Med. 31:299–304, 2002. © 2002 Wiley‐Liss, Inc.
Response to a lethal dose of heat shock by a transient up‐regulation of clusterin expression followed by down‐regulation and apoptosis in prostate and bladder cancer cells
Authors: Wu Angela J. , Park Irwin I. , Zhaung Lei , Lee Chung
Published: November 2002

BACKGROUND

Clusterin is a ubiquitous, secretory glycoprotein with a wide array of functions. Recent studies have implicated that clusterin functioned as heat shock response proteins. The objective of the present study was to determine the fate of clusterin expression in cancer cells, which were subjected to a lethal dose of heat shock, in an attempt to shed light on mechanisms of action of clusterin.

METHODS

A prostate cancer line, PC‐3, and a bladder cancer line, TSU‐Pr1, were selected owing to their aggressive growth behaviors. Apoptosis was assessed by enzymatic activities of terminal deoxynucleotidyl transferase as well as by activities of caspase‐3. Cells were exposed to 45°C for a period of 60 min.

RESULTS

Both cell lines underwent a transient up‐regulation of clusterin expression followed by down‐regulation and apoptosis. TSU‐Prl cells produced higher levels of clusterin and displayed a greater resistance to apoptosis than did PC‐3 cells. The addition of exogenous clusterin to the cultures of PC‐3 cells protected apoptosis. Treatment of oligonucleotide antisense to clusterin to the cultures of TSU‐Pr1 cells enhanced apoptosis mediated by heat shock.

CONCLUSION

Clusterin offers a protection to PC‐3 and TSU‐Prl cells against heat shock and plays an important role in the cascade of events initiated by heat shock. Prostate 53: 277–285, 2002. © 2002 Wiley‐Liss, Inc.
Medical Pediatric Psychology Has Come of Age
Authors: Dewey Deborah
Published: November 2002

In the last line of the forward to Pediatric
Neuropsychology, Arthur Benton stated that “pediatric
neuropsychology has come of age.” This volume provides
ample support for this statement. It demonstrates how the field
of pediatric neuropsychology has developed and matured, but
it also reminds us of the many questions that remain unanswered.
Its focus is on the neurobehavioral sequelae of various medical
disorders such as epilepsy, meningitis, and diabetes. It does
not address, however, the neurobehavioral outcomes associated
with attention-deficit/hyperactivity disorder, learning
disabilities and autism spectrum disorders. As indicated by
Byron Rourke in his commentary (chapter 20), “these are
important areas of pediatric neuropsychological research that
merit attention because of their theoretical and clinical
relevance” (p. 476). I agree with Dr. Rourke's statement
that they should be covered in a book that deals with pediatric
neuropsychology and would also encourage the editors to include
them in a second edition should it be forthcoming. Despite this
shortcoming, this book is an excellent reference for both
researchers and clinicians in pediatric neuropsychology. Further,
because of its multidisciplinary nature it may be of interest
to other professionals who work with and treat children with
various medical disorders that have neurobehavioral sequelae
such as pediatricians, pediatric neurologists, pediatric
psychiatrists and medical geneticists.
Interrater reliability of neuropsychological diagnoses: A
Department of Veterans Affairs cooperative study
Authors: WHITE ROBERTA F. , JAMES KENNETH E. , VASTERLING JENNIFER J. , MARANS KAREN , DELANEY RICHARD , KRENGEL MAXINE , ROSE FREDRIC
Published: November 2002

This study examined the interrater reliability of
neuropsychological diagnoses produced by clinical
neuropsychologists across 4 medical centers. These diagnoses
were based on evaluations using a comprehensive battery of commonly
used neuropsychological test instruments, interview, history
and medical chart review. The diagnoses of individual
neuropsychologists were compared to those made by members of
an external review panel for each patient evaluated. Patients
were first diagnosed as showing cognitive impairment
versus no cognitive impairment. If a patient was diagnosed
as impaired, a specific neuropsychological diagnosis was assigned.
The diagnostic classification for cognitive impairment was
moderately reliable [κ = .48 ± s.e.(κ) = .062].
The interrater reliability for specific diagnoses was in the fair to
good range [κ = .44 ± s.e.(κ) = .029].
These levels of reliability are comparable to those found for
other psychiatric and neurologic specialties and for medical
diagnoses made by other health care disciplines. (JINS,
2002, 8, 555–565.)
Neurodevelopmental outcome for extended cold water drowning:
A longitudinal case study
Authors: HUGHES SUSANNAH KURY , NILSSON DAVID E. , BOYER RICHARD S. , BOLTE ROBERT G. , HOFFMAN ROBERT O. , LEWINE JEFFERY D. , BIGLER ERIN D.
Published: November 2002

There is little longitudinal data examining outcome of pediatric
near-drowning. Most literature tracks status 5 years or less
post insult, focusing primarily on gross neurologic status as
opposed to more subtle neurocognitive deficits. The present
case tracks the neuropsychological profile of a child who was
submerged for 66 min, the longest time documented. Acute medical
support was aggressive, and recovery was dramatic, being featured
in multiple media reports. Although an article published 6 years
after the near-drowning described the child as “recovering
completely,” the longitudinal profile indicates a pronounced
pattern of broad cognitive difficulties, particularly notable
for global memory impairment. Neuropsychological test results
were significant despite the fact that the patient's recent
MRI and MEG were within normal limits. This case demonstrates
the need for long-term neuropsychological follow-up of pediatric
patients with histories of neurologic injury, as gross neurological
examination and MRI and MEG scans may not reveal underlying
brain dysfunction. (JINS, 2002, 8, 588–595.)
Immediate versus sustained processing in schizophrenia
Authors: SALO RUTH , HENIK AVISHAI , NORDAHL THOMAS E. , ROBERTSON LYNN C.
Published: November 2002

A Stroop negative priming (NP) task was used to assess immediate
selective attention and priming in schizophrenia and
schizoaffective disorder. Subject groups were comprised of 12
state hospital inpatients (41.8 ± 7.5 years of age),
11 outpatients (39.8 ± 7.5 years of age), and 16 controls
(36.4 ± 11.7 years of age). Compared with the control
group and the outpatients, inpatients failed to exhibit NP
[F(2,36) = 6.09, p < .01],
despite exhibiting equivalent Stroop RT interference (p
> .05). Error rates did not differ significantly between
the 3 groups. Although medication types and dosages were similar
between the 2 patient groups, length of illness was significantly
longer in the inpatients (19.8 years) than in the outpatients
(12.4 years; p < .05). Positive symptom ratings
were also significantly higher in the inpatients. The finding
of reduced NP in the state hospital patients appears to be related
to severity of symptomatology and chronicity of illness.
(JINS, 2002, 8, 794–803.)
Dementia with Lewy bodies may present as dementia and REM
sleep behavior disorder without parkinsonism or hallucinations
Authors: FERMAN TANIS J. , BOEVE BRADLEY F. , SMITH GLENN E. , SILBER MICHAEL H. , LUCAS JOHN A. , GRAFF-RADFORD NEILL R. , DICKSON DENNIS W. , PARISI JOSEPH E. , PETERSEN RONALD C. , IVNIK ROBERT J.
Published: November 2002

Rapid eye movement (REM) sleep behavior disorder (RBD) is a
sleep disturbance that commonly occurs in Dementia with Lewy
bodies (DLB). Retrospective examination of DLB course has shown
that RBD and cognitive decline may precede the onset of
parkinsonism and visual hallucinations. Therefore, some patients
with DLB may initially present with dementia and RBD, but would
not meet current formal criteria for probable DLB at that time.
The purpose of this study is to determine whether patients with
dementia and RBD, who do not have parkinsonism or visual
hallucinations, have cognitive profiles that can be distinguished
from autopsy-confirmed definite AD, but not from clinically
probable DLB. If so, this would support the hypothesis that
the presence of RBD and dementia, as the only presenting symptoms,
reflects the early manifestation of DLB. Results show that early
dementia in probable DLB and dementia with RBD are
neuropsychologically indistinguishable. Both groups differ from
definite AD of a similar early stage with significantly worse
visual perceptual organization, sequencing and letter fluency
but significantly better confrontation naming and verbal memory.
In addition, follow-up data from a subset of patients with dementia
and RBD reveal the subsequent development of parkinsonism or
hallucinations 1 to 6 years later. Results indicate that the
presentation of dementia and RBD is suggestive of underlying
Lewy body disease and not Alzheimer's disease. This provides
further evidence in support of including RBD as one of the core
diagnostic features of DLB. (JINS, 2002, 8, 907–914.)
Decline in verbal memory during preclinical Alzheimer's
disease: Examination of the effect of APOE genotype
Authors: LANGE KELLY L. , BONDI MARK W. , SALMON DAVID P. , GALASKO DOUGLAS , DELIS DEAN C. , THOMAS RONALD G. , THAL LEON J.
Published: November 2002

A subtle decline in episodic memory often occurs prior to the
emergence of the full dementia syndrome in nondemented older
adults who develop Alzheimer's disease (AD). The APOE-ε4
genotype may engender a more virulent form of AD that hastens
this decline. To examine this possibility, we compared the rate
of decline in episodic memory during the preclinical phase of
AD in individuals with or without at least one APOE ε4 allele.
Nondemented normal control (NC; n = 84) participants,
nondemented older adults who subsequently developed dementia
within 1 or 2 years (i.e., preclinical AD; n = 20),
and patients with mild AD (n = 53) were examined with 2
commonly employed tests of episodic memory, the Logical Memory
subtest of the Wechsler Memory Scale–Revised and the California
Verbal Learning Test. Results revealed a precipitous decline in verbal
memory abilities 1 to 2 years prior to the onset of the dementia syndrome,
but there was little effect of APOE genotype on the rate of this
memory decline. The presence of an APOE-ε4 allele, however,
did have a differential effect on the sensitivity of the 2 types
of memory tests for tracking progression and made an independent
contribution to the prediction of conversion to AD. (JINS,
2002, 8, 943–955.)
A Legal Primer for Neuropsychologists?
Authors: Varney Nils R.
Published: November 2002

The editors of this book state in the Preface that
“this volume is not a ‘how to guidebook.’
” While this is certainly true, the chapters explaining
legal issues (e.g., rules of evidence) offer what is essentially
an advanced primer on evidentiary law as it relates to
psychological testimony in civil and criminal trials. It
is in this regard that the work has its greatest value.
The Canalicular Structure of Compact Bone in the Rat at
Different Ages
Authors: Okada Shigenori , Yoshida Shigemitsu , Ashrafi Shahid H. , Schraufnagel Dean E.
Published: November 2002

Osteocytes communicate through a canalicular system that maintains
the vitality and mineral metabolism of bone. Casting the vascular
canals and canaliculi of compact bone with methacrylate and
viewing them with scanning electron microscopy shows their extent
and relationships. Confocal laser scanning microscopy of the
same specimen before corrosion establishes the degree of
calcification of the different tissue components. These methods
were used to compare basal with alveolar compact bone in the
rat mandible at different ages. Sections of the mandibular molar
region were placed in a methacrylate resin. After polymerization
and study with confocal microscopy, the organic matrix was removed.
Juvenile rats had large irregular central vascular canals and
lacunae that were more concentric in the basal than the alveolar
bone. Cast lacunae were round, and the canaliculi from these
lacunae were short and thick in both bones. Adult rats had regular
concentrically arranged lacunae in the basal bone. Cast lacunae
were ellipsoid and flatter in the basal bone than in the alveolar
bone. The intercommunicating canaliculi were increased and
canaliculi had more branching than the juvenile rats. The aged
rats had fewer vascular canals, lacunae, and canaliculi and
had osteoporotic changes. The cast lacunae were slender and
flat especially in the basal bone. The porosity of the mandible
became more pronounced in the alveolar than in the basal bone
with aging. The canaliculi of mandibular compact bone thinned
and developed extensive branching with adulthood but decreased
in size and number with advanced age. Lacunae proceed from the
large circular structures of youth to the flat forms of the
aged. These studies show that the internal structure of compact
bone changes with age and mirrors its functional state.
New Applications of Electron Diffraction in the Pharmaceutical
Industry: Polymorph Determination by Using a Combination of
Electron Diffraction and Synchrotron X-ray Powder Diffraction
Techniques
Authors: Li Z.G. , Harlow R.L. , Foris C.M. , Li H. , Ma P. , Vickery R.D. , Maurin M.B. , Toby B.H.
Published: November 2002

Electron diffraction has been recently used in the pharmaceutical
industry to study the polymorphism in crystalline drug substances.
While conventional X-ray diffraction patterns could not be used
to determine the cell parameters of two forms of the
microcrystalline GP IIb/IIIa receptor antagonist roxifiban,
a combination of electron single-crystal and synchrotron powder
diffraction techniques were able to clearly distinguish the
two polymorphs. The unit-cell parameters of the two polymorphs
were ultimately determined using new software routines designed
to take advantage of each technique's unique capabilities.
The combined use of transmission electron microscopy (TEM) and
synchrotron patterns appears to be a good general approach for
characterizing complex (low-symmetry, large-unit-cell,
micron-sized) polymorphic pharmaceutical compounds.
Chemistry with the Electron Microscope: Some Highlights in
a Lifetime's Journey
Authors: Thomas John Meurig
Published: November 2002

The supreme advantages of electron microscopy (EM) in the chemical
sciences are briefly recalled: By judicious use of electron
optical techniques, vital information of a structural, mechanistic,
compositional, and often of an electronic kind may be retrieved.
Not only are insights gained (through EM) into the existence
of whole new families of structures hitherto unperceived, but
one also uncovers the structural characteristics of imperfections
in solids. And it is often the case that these imperfections
reflect or suggest altogether new structures, hitherto unconceived.
EM is, therefore, a powerful agent for aiding chemical synthesis
of new materials. This is particularly important in the field
of heterogeneous catalysis, since altogether new types of catalytic
materials may be, on the one hand, defined, described, identified,
and characterised, and, on the other, designed and synthesised.
There is also the ever-improving role of the electron microscope
as an analytical tool: Very few other techniques within reach
of the chemist can rival it in its sensitivity and detection
limits. (Scanning instruments now permit the imaging and the
identification of nanoclusters consisting of just a few atoms.)
But there are numerous other branches of chemistry besides
catalysis and surface science where EM proves invaluable, as
we outline herein, in elucidating structure–property or
composition and structure interrelationships.
Transmission Electron Microscopy Studies of the Nanoscale
Structure and Chemistry of Pt50Ru50
Electrocatalysts
Authors: Stroud Rhonda M. , Long Jeffrey W. , Swider-Lyons Karen E. , Rolison Debra R.
Published: November 2002

The structural and chemical heterogeneity of 2.5-nm
Pt50Ru50 electrocatalysts was studied
by transmission electron microscopy using selected area
diffraction, lattice imaging, electron-energy loss spectroscopy,
and energy-dispersive X-ray spectroscopy. The catalysts with
the highest methanol oxidation activities exhibit oxidation-induced
phase separation on the nanoscale to form Pt-rich metal embedded
in Ru-rich hydrous and anhydrous oxide. Reduction of the
oxide-on-metal samples produces a true bimetallic face-centered
cubic Pt50Ru50 alloy, with 275 times lower
oxidation activity.
Integration of Cot Analysis, DNA Cloning, and High-Throughput Sequencing Facilitates Genome Characterization and Gene Discovery
Authors: Peterson Daniel G. , Schulze Stefan R. , Sciara Erica B. , Lee Scott A. , Bowers John E. , Nagel Alexander , Jiang Ning , Tibbitts Deanne C. , Wessler Susan R. , Paterson Andrew H.
Published: November 2002

Cot-based sequence discovery represents a powerful means by which both low-copy and repetitive sequences can be selectively and efficiently fractionated, cloned, and characterized. Based upon the results of a Cot analysis, hydroxyapatite chromatography was used to fractionate sorghum (Sorghum bicolor) genomic DNA into highly repetitive (HR), moderately repetitive (MR), and single/low-copy (SL) sequence components that were consequently cloned to produce HRCot, MRCot, and SLCot genomic libraries. Filter hybridization (blotting) and sequence analysis both show that the HRCot library is enriched in sequences traditionally found in high-copy number (e.g., retroelements, rDNA, centromeric repeats), the SLCot library is enriched in low-copy sequences (e.g., genes and “nonrepetitive ESTs”), and the MRCot library contains sequences of moderate redundancy. The Cot analysis suggests that the sorghum genome is approximately 700 Mb (in agreement with previous estimates) and that HR, MR, and SL components comprise 15%, 41%, and 24% of sorghum DNA, respectively. Unlike previously described techniques to sequence the low-copy components of genomes, sequencing of Cot components is independent of expression and methylation patterns that vary widely among DNA elements, developmental stages, and taxa. High-throughput sequencing of Cot clones may be a means of “capturing” the sequence complexity of eukaryotic genomes at unprecedented efficiency.

[Online supplementary material is available at www.genome.org. The sequence data described in this paper have been submitted to the GenBank under accession nos.AZ921847-AZ923007. Reagents, samples, and unpublished information freely provided by H. Ma and J. Messing.]
Identification of Candidate Genes Regulating HDL Cholesterol Using a Chromosomal Region Expression Array
Authors: Cox Laura A. , Birnbaum Shifra , VandeBerg John L.
Published: November 2002

To identify candidate genes encoding QTLs in baboons, we have developed a novel strategy that integrates comparative mapping, bioinformatics, and expression arrays. A genome-wide scan, performed previously on pedigreed baboons to localize QTLs for phenotypes that are known risk factors for atherosclerosis, revealed a QTL on chromosome 18q that influences high-density lipoprotein cholesterol (HDL-C) phenotypes. After ruling out the only two biologically relevant positional candidate genes in this chromosomal region, we combined information from baboon pedigrees and HDL-C phenotypes with a baboon microsatellite marker map, human microsatellite marker maps, and human genome maps to develop a chromosomal region expression array (CREA). The CREA was screened with heterologous liver cDNA from sib-pairs of contrasting HDL-C phenotypes on two different diets, and genes were prioritized for further study by expression profiles. Analysis of gene expression in this restricted chromosomal region, combined with HDL-C phenotypic information, yielded a list of candidate genes for the QTL regulating HDL-C in baboons. Our data demonstrate the power of this strategy for identifying candidate genes encoding QTLs for multigenic traits. This strategy is applicable to many species that serve as models for human diseases and can even be used with human subjects.
Protein–Protein Interactions Between Large Proteins: Two-Hybrid Screening Using a Functionally Classified Library Composed of Long cDNAs
Authors: Nakayama Manabu , Kikuno Reiko , Ohara Osamu
Published: November 2002

Large proteins have multiple domains that are potentially capable of binding many kinds of partners. It is conceivable, therefore, that such proteins could function as an intricate framework of assembly protein complexes. To comprehensively study protein–protein interactions between large KIAA proteins, we have constructed a library composed of 1087 KIAA cDNA clones based on prior functional classifications done in silico. We were guided by two principles that raise the success rate for detecting interactions per tested combination: we avoided testing low-probability combinations, and reduced the number of potential false negatives that arise from the fact that large proteins cannot reliably be expressed in yeast. The latter was addressed by constructing a cDNA library comprised of random fragments encoding large proteins. Cytoplasmic domains of KIAA transmembrane proteins (>1000 amino acids) were used as bait for yeast two-hybrid screening. Our analyses reveal that several KIAA proteins bearing a transmembrane region have the capability of binding to other KIAA proteins containing domains (e.g., PDZ, SH3, rhoGEF, and spectrin) known to be localized to highly specialized submembranous sites, indicating that they participate in cellular junction formation, receptor or channel clustering, and intracellular signaling events. Our representative library should be a very useful resource for detecting previously unidentified interactions because it complements conventional expression libraries, which seldom contain large cDNAs.

[Interaction data accession numbers are BIND ID 12487–12570. Supplemental material is available online athttp://www.genome.org.]
Large-Scale Proteomic Analysis of the Human Spliceosome
Authors: Rappsilber Juri , Ryder Ursula , Lamond Angus I. , Mann Matthias
Published: November 2002

In a previous proteomic study of the human spliceosome, we identified 42 spliceosome-associated factors, including 19 novel ones. Using enhanced mass spectrometric tools and improved databases, we now report identification of 311 proteins that copurify with splicing complexes assembled on two separate pre-mRNAs. All known essential human splicing factors were found, and 96 novel proteins were identified, of which 55 contain domains directly linking them to functions in splicing/RNA processing. We also detected 20 proteins related to transcription, which indicates a direct connection between this process and splicing. This investigation provides the most detailed inventory of human spliceosome-associated factors to date, and the data indicate a number of interesting links coordinating splicing with other steps in the gene expression pathway.
CpG Methylation Modifies the Genetic Stability of Cloned Repeat Sequences
Authors: Nichol Kerrie , Pearson and Christopher E.
Published: November 2002

The genetic stability of tandemly repeated DNAs is affected by repeat sequence, tract length, tract purity, and replication direction. Alterations in DNA methylation status are thought to influence many processes of mutagenesis. By use of bacterial and primate cell systems, we have determined the effect of CpG methylation on the genetic stability of cloned di-, tri-, penta- and minisatellite repeated DNA sequences. Depending on the repeat sequence, methylation can significantly enhance or reduce its genetic stability. This effect was evident when repeat tracts were replicated from either direction. Unexpectedly, methylation of adjacent sequences altered the stability of contiguous repeat sequences void of methylatable sites. Of the seven repeat sequences investigated, methylation stabilized five, destabilized one, and had no effect on another. Thus, although methylation generally stabilized repeat tracts, its influence depended on the sequence of the repeat. The current results lend support to the notion that the biological consequences of CpG methylation may be affected through local alterations of DNA structure as well as through direct protein–DNA interactions. In vivo CpG methylation in bacteria may have technical applications for the isolation and stable propagation of DNA sequences that have been recalcitrant to isolation and/or analyses because of their extreme instability.

[Supplementary material available online athttp://www.genome.org.]
Physical Maps for Genome Analysis of Serotype A and D Strains of the Fungal Pathogen Cryptococcus neoformans
Authors: Schein Jacqueline E. , Tangen Kristin L. , Chiu Readman , Shin Heesun , Lengeler Klaus B. , MacDonald William Kim , Bosdet Ian , Heitman Joseph , Jones Steven J.M. , Marra Marco A. , Kronstad James W.
Published: November 2002

The basidiomycete fungus Cryptococcus neoformans is an important opportunistic pathogen of humans that poses a significant threat to immunocompromised individuals. Isolates of C. neoformans are classified into serotypes (A, B, C, D, and AD) based on antigenic differences in the polysaccharide capsule that surrounds the fungal cells. Genomic and EST sequencing projects are underway for the serotype D strain JEC21 and the serotype A strain H99. As part of a genomics program for C. neoformans, we have constructed fingerprinted bacterial artificial chromosome (BAC) clone physical maps for strains H99 and JEC21 to support the genomic sequencing efforts and to provide an initial comparison of the two genomes. The BAC clones represented an estimated 10-fold redundant coverage of the genomes of each serotype and allowed the assembly of 20 contigs each for H99 and JEC21. We found that the genomes of the two strains are sufficiently distinct to prevent coassembly of the two maps when combined fingerprint data are used to construct contigs. Hybridization experiments placed 82 markers on the JEC21 map and 102 markers on the H99 map, enabling contigs to be linked with specific chromosomes identified by electrophoretic karyotyping. These markers revealed both extensive similarity in gene order (conservation of synteny) between JEC21 and H99 as well as examples of chromosomal rearrangements including inversions and translocations. Sequencing reads were generated from the ends of the BAC clones to allow correlation of genomic shotgun sequence data with physical map contigs. The BAC maps therefore represent a valuable resource for the generation, assembly, and finishing of the genomic sequence of both JEC21 and H99. The physical maps also serve as a link between map-based and sequence-based data, providing a powerful resource for continued genomic studies.

[This paper is dedicated to the memory of Michael Smith, Founding Director of the Biotechnology Laboratory and the BC Cancer Agency Genome Sciences Centre. Supplemental material is available online at http://www.genome.org.]