bluuebunny/crossref_metadata_2025 huggingface dataset:
Matrix Metalloproteinases (MMPs) Regulate Fibrin-invasive Activity via MT1-MMP–dependent and –independent Processes
Authors: Hotary Kevin B. , Yana Ikuo , Sabeh Farideh , Li Xiao-Yan , Holmbeck Kenn , Birkedal-Hansen Henning , Allen Edward D. , Hiraoka Nobuaki , Weiss Stephen J.
Published: July 2002

Cross-linked fibrin is deposited in tissues surrounding wounds, inflammatory sites, or tumors and serves not only as a supporting substratum for trafficking cells, but also as a structural barrier to invasion. While the plasminogen activator-plasminogen axis provides cells with a powerful fibrinolytic system, plasminogen-deleted animals use alternate proteolytic processes that allow fibrin invasion to proceed normally. Using fibroblasts recovered from wild-type or gene-deleted mice, invasion of three-dimensional fibrin gels proceeded in a matrix metalloproteinase (MMP)-dependent fashion. Consistent with earlier studies supporting a singular role for the membrane-anchored MMP, MT1-MMP, in fibrin-invasive events, fibroblasts from MT1-MMP–null mice displayed an early defect in invasion. However, MT1-MMP–deleted fibroblasts circumvented this early deficiency and exhibited compensatory fibrin-invasive activity. The MT1-MMP–independent process was sensitive to MMP inhibitors that target membrane-anchored MMPs, and further studies identified MT2-MMP and MT3-MMP, but not MT4-MMP, as alternate pro-invasive factors. Given the widespread distribution of MT1-, 2-, and 3-MMP in normal and neoplastic cells, these data identify a subset of membrane-anchored MMPs that operate in an autonomous fashion to drive fibrin-invasive activity.
The Effect of Novel Attributes on Product Evaluation
Authors: Mukherjee Ashesh , Hoyer Wayne D.
Published: July 2002

Many technological innovations introduce attributes that are novel or completely unknown to a large number of consumers. For example, recently introduced attributes such as GPS in cars or I-Link in computers are likely to have been novel to many consumers. Past research suggests that the addition of novel attributes is likely to improve product evaluation and sales, since consumers interpret these attributes as additional benefits provided by the manufacturer. However, this article demonstrates that the positive effect of novel attributes holds only in the case of low-complexity products. In the case of high-complexity products, the addition of novel attributes can actually reduce product evaluation because of negative learning-cost inferences about these attributes. Further, the positive and negative effects of novel attributes on product evaluation are accentuated by external search for information when the information discovered through search is ambiguous in nature. Finally, it is shown that the negative effect of novel attributes on the evaluation of high-complexity products can persist even after consumers are given explicit information about the benefits of novel attributes. A key marketing implication of these findings is that novel attributes may contribute to technophobia, or consumer resistance toward technological innovation.
Geometric properties of the sections of solutions to the Monge-Ampère equation
Authors: Gutiérrez Cristian , Huang Qingbo
Published: July 2002

In this paper we establish several geometric properties of the cross sections of generalized solutions

ϕ
\phi

to the Monge-Ampère equation

det

D

2

ϕ
=
μ

\det D^{2}\phi = \mu

, when the measure

μ
\mu

satisfies a doubling property. A main result is a characterization of the doubling measures

μ
\mu

in terms of a geometric property of the cross sections of

ϕ
\phi

. This is used to obtain estimates of the shape and invariance properties of the cross sections that are valid under appropriate normalizations.
Subgroups of 𝐺𝐿(𝑛²,𝐂) containing 𝐏𝐒𝐔(𝐧)
Authors: Platonov V. , Đoković D.
Published: July 2002

Let

P
S
U

(
n
)

\mathrm {PSU}(n)

be the image of the unitary group

U

(
n
)

\mathrm {U}(n)

under the representation

x
→
a
x

a

−
1

x\to axa^{-1}

on the space

M
n

(

C

)

M_n(\mathbf {C} )

of

n
n

by

n
n

complex matrices. We classify all connected Lie subgroups of

G
L

(

n
2

,

C

)

\mathrm {GL}(n^2,\mathbf {C} )

containing

P
S
U

(
n
)

\mathrm {PSU}(n)

. We use this result to obtain a description of all abstract overgroups of

P
S
U

(
n
)

\mathrm {PSU}(n)

in

G
L

(

n
2

,

C

)

\mathrm {GL}(n^2,\mathbf {C} )

. We apply this classification to solve the problem of describing all invertible linear transformations of

M
n

(

C

)

M_n(\mathbf {C} )

which preserve the set of normal matrices. Our results can be applied to solve many other problems of similar nature.
Doodle groups
Authors: Khovanov Mikhail
Published: July 2002

A doodle is a finite number of closed curves without triple intersections on an oriented surface. There is a “fundamental” group, naturally associated with a doodle. In this paper we study these groups, in particular, we show that fundamental groups of some doodles are automatic and give examples of doodles whose fundamental groups have non-trivial center.
Eigenvalues of periodic Sturm-Liouville problems by the Shannon-Whittaker sampling theorem
Authors: Boumenir Amin
Published: July 2002

We are concerned with the computation of eigenvalues of a periodic Sturm-Liouville problem using interpolation techniques in Paley-Wiener spaces. We shall approximate the Hill discriminant by sampling a few of its values and then find its zeroes which are the square roots of the eigenvalues. Computable error estimates are provided together with eigenvalue enclosures.
Longest increasing subsequences: from patience sorting to the Baik-Deift-Johansson theorem
Authors: Aldous David , Diaconis Persi
Published: July 2002

We describe a simple one-person card game, patience sorting. Its analysis leads to a broad circle of ideas linking Young tableaux with the longest increasing subsequence of a random permutation via the Schensted correspondence. A recent highlight of this area is the work of Baik-Deift-Johansson which yields limiting probability laws via hard analysis of Toeplitz determinants.
Order 𝑝 automorphisms of the open disc of a 𝑝-adic field
Authors: Green Barry , Matignon Michel
Published: July 2002

Let

k
k

be an algebraically closed field of characteristic

p
>
0
,

p>0,

W
(
k
)

W(k)

the ring of Witt vectors and

R
R

a complete discrete valuation ring dominating

W
(
k
)

W(k)

and containing

ζ
,

\zeta ,

a primitive

p
p

-th root of unity. Let

π
\pi

denote a uniformizing parameter for

R
.

R.

We study order

p
p

automorphisms of the formal power series ring

R
[
[
Z
]
]
,

R[[Z]],

which are defined by a series
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="sigma left-parenthesis upper Z right-parenthesis equals zeta upper Z left-parenthesis 1 plus a 1 upper Z plus midline-horizontal-ellipsis plus a Subscript i Baseline upper Z Superscript i Baseline plus midline-horizontal-ellipsis right-parenthesis element-of upper R left-bracket left-bracket upper Z right-bracket right-bracket period">

σ
(
Z
)
=
ζ
Z
(
1
+

a

1

Z
+
⋯
+

a

i

Z

i

+
⋯
)
∈
R
[
[
Z
]
]
.

\begin{equation*}\sigma (Z)=\zeta Z(1+a_{1}Z+\cdots +a_{i}Z^{i}+\cdots )\in R[[Z]].\end{equation*}

The set of fixed points of

σ
\sigma

is denoted by

F

σ

F_{\sigma }

and we suppose that they are

K
K

-rational and that

|

F

σ

|

=
m
+
1

|F_{\sigma }|=m+1

for

m
≥
0.

m\geq 0.

Let

D

o

{\mathcal {D}}^{o}

be the minimal semi-stable model of the

p
p

-adic open disc over

R
R

in which

F

σ

F_{\sigma }

specializes to distinct smooth points. We study the differential data that can be associated to each irreducible component of the special fibre of

D

o

.

{\mathcal {D}}^{o}.

Using this data we show that if

m
>
p

m>p

, then the fixed points are equidistant, and that there are only a finite number of conjugacy classes of order

p
p

automorphisms in

Aut

R

⁡
(
R
[
[
Z
]
]
)

\operatorname {Aut}_{R}(R[[Z]])

which are not the identity

mod
⁡
(
π
)
.

\operatorname {mod} (\pi ).
Real algebraic threefolds II. Minimal model program
Authors: Kollár János
Published: July 2002

This is the second of a series of papers studying real algebraic threefolds using the minimal model program. The main result is the following. LetXXbe a smooth projective real algebraic 3-fold. Assume that the set of real points is an orientable 3-manifold (this assumption can be weakened considerably). Then there is a fairly simple description of how the topology of real points changes under the minimal model program. This leads to the solution of the Nash conjecture concerning the topology of real projective varieties which are birational to projective 3-space. Another application is a factorization theorem for birational maps.
Targeting of Rough Endoplasmic Reticulum Membrane Proteins and Ribosomes in Invertebrate Neurons
Authors: Rolls Melissa M. , Hall David H. , Victor Martin , Stelzer Ernst H. K. , Rapoport Tom A.
Published: July 2002

The endoplasmic reticulum (ER) is divided into rough and smooth domains (RER and SER). The two domains share most proteins, but RER is enriched in some membrane proteins by an unknown mechanism. We studied RER protein targeting by expressing fluorescent protein fusions to ER membrane proteins in Caenorhabditis elegans. In several cell types RER and general ER proteins colocalized, but in neurons RER proteins were concentrated in the cell body, whereas general ER proteins were also found in neurites. Surprisingly RER membrane proteins diffused rapidly within the cell body, indicating they are not localized by immobilization. Ribosomes were also concentrated in the cell body, suggesting they may be in part responsible for targeting RER membrane proteins.
Repeated Hospitalizations and Self-rated Health among the Elderly: A Multivariate Failure Time Analysis
Authors: Kennedy Byron S. , Kasl Stanislav V. , Vaccarino Viola
Published: July 2002

The purpose of this study was to determine to what extent a single measure, self-rated health (SRH), independently predicts long-term hospitalizations due to all causes and to cardiovascular diseases by using both the standard Cox proportional hazards model and a more robust events model. The study cohort consisted of 2,812 elderly subjects residing in New Haven, Connecticut, who were followed from 1982 to 1996 as part of the Established Populations for Epidemiologic Study of the Elderly. After adjustment for baseline risk factors, using the Cox model, a favorable SRH was associated with a significantly lowered risk for a first hospitalization for all causes (risk ratio (RR) = 0.850, 95% confidence interval (CI): 0.774, 0.934) and congestive heart failure (RR = 0.599, 95% CI: 0.426, 0.841) but not for myocardial infarction (RR = 0.882, 95% CI: 0.565, 1.379). With the adjusted robust events model, a positive SRH was associated with a decreased risk in both a first (RR = 0.813, 95% CI: 0.744, 0.889) and a second (RR = 0.870, 95% CI: 0.782, 0.968) hospitalization for any cause. These results indicate that a single measurement of SRH predicts long-term patterns of hospitalization, especially for heart failure, among older adults.
Association between Physical Activity and Markers of Inflammation in a Healthy Elderly Population
Authors: Geffken Dominic F. , Cushman Mary , Burke Gregory L. , Polak Joseph F. , Sakkinen Pamela A. , Tracy Russell P.
Published: July 2002

Higher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989–1990 and 1992–1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged ≥65 years, were analyzed. Concentrations of the inflammation markers–C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin–were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19%, 6%, 4%, and 3% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.
Menstrual History and Risk of Hip Fractures in Postmenopausal Women The Iowa Women's Health Study
Authors: Nicodemus Kristin K. , Folsom Aaron R. , Anderson Kristin E.
Published: July 2002

The authors examined prospectively between 1986 and 1997 the relation of irregular menstrual cycles and irregular menstrual bleeding duration earlier in life with risk of hip fracture in 33,434 postmenopausal Iowa women. Over the 318,522 person-years of follow-up, 523 hip fractures were reported. Adjusted for age, smoking, body mass index, waist/hip ratio, and estrogen use, the relative risk of hip fracture in women who reported always having irregular menstrual cycles, compared with women who never had irregular cycles, was 1.36 (95% confidence interval (CI): 1.03, 1.78). Women who reported having irregular menstrual bleeding duration had a 1.40-fold (95% CI: 1.10, 1.78) increased risk of hip fracture compared with women with regular bleeding duration. In addition, women who reported having both irregular menstrual cycles and irregular menstrual bleeding had a 1.82-fold (95% CI: 1.55, 2.15) higher risk of hip fracture than did women who reported neither irregularity. Women who reported only one menstrual disturbance did not have a risk of hip fracture that was significantly different from women who reported no menstrual disturbances. The authors conclude that women with menstrual irregularities are at increased risk of hip fracture, probably because they are estrogen or progesterone deficient.
Maternal Exposure to Nitrate from Drinking Water and Diet and Risk for Neural Tube Defects
Authors: Croen Lisa A. , Todoroff Karen , Shaw Gary M.
Published: July 2002

In this population-based case-control study conducted in California between June 1989 and May 1991, the authors investigated the association between maternal periconceptional exposure to nitrate from drinking water and diet and risk for neural tube defects. The mothers of 538 cases and 539 nonmalformed controls were interviewed regarding residential history, consumption of tap water at home, and dietary intake during the periconceptional period. Dietary nitrate exposure was not associated with increased risk for neural tube defects. Exposure to nitrate in drinking water at concentrations above the 45 mg/liter maximum contaminant level was associated with increased risk for anencephaly (odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.0, 15.4), but not for spina bifida. Increased risks for anencephaly were observed at nitrate levels below the maximum contaminant level among groundwater drinkers only (OR = 2.1, 95% CI: 1.1, 4.1 for 5–15 mg/liter; OR = 2.3, 95% CI: 1.1, 4.5 for 16–35 mg/liter; and OR = 6.9, 95% CI: 1.9, 24.9 for 36–67 mg/liter compared with <5 mg/liter). Adjustment for identified risk factors for anencephaly did not substantially alter these associations, nor did control for maternal dietary nitrate, total vitamin C intake, and quantity of tap water consumed. The lack of an observed elevation in risk for anencephaly in association with exposure to mixed water containing nitrate at levels comparable with the concentration in groundwater may indicate that something other than nitrate accounts for these findings.
Fingerprint Ridge-Count Difference between Adjacent Fingertips (dR45) Predicts Upper-Body Tissue Distribution: Evidence for Early Gestational Programming
Authors: Kahn Henry S. , Ravindranath Roopa , Valdez Rodolfo , Venkat Narayan K. M.
Published: July 2002

Fingerprint ridge counts, which remain constant from the 19th week of pregnancy, are related to fingertip growth during early gestation. Each finger corresponds neurologically to a spinal-cord segment ranging from C6 (thumb, relatively cephalad) to C8 (fifth finger, relatively caudad). The authors hypothesized that large ridge-count differences between fingertips (cephalad > caudad) might reflect fetal inhibition of caudal growth. Among 69 male Atlanta, Georgia, military recruits (1994–1997; aged 17–22 years), they tested associations of the anthropometric waist-to-thigh ratio with 20 ridge-count differences. Waist-to-thigh ratio was associated with the ridge-count difference between the right fourth and fifth fingertips only (dR45; r = 0.36, p = 0.003). The race-adjusted standardized regression coefficient was 0.22 (95% confidence interval: 0.03, 0.41). Since upper-body tissue distribution indicates disease risk, the authors then tested the association of age (an indicator of survivorship) with dR45 in a sample of 135 male patients from Bangalore, India (1989–1990; aged 38–82 years). Age was inversely associated with dR45 (r = −0.17, p = 0.04), notably among the 75 men with diabetes (r = −0.22, p = 0.06). An increased dR45 predicts an upper-body tissue distribution originating before the midpoint of pregnancy. The cause of this developmental pattern is unknown, but it may lead to reduced survivorship.
Coffee Consumption and Serum Lipids: A Meta-Analysis of Randomized Controlled Clinical Trials
Authors: Jee Sun Ha , He Jiang , Appel Lawrence J. , Whelton Paul K. , Suh II , Klag Michael J.
Published: July 2002

Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.
Invited Commentary: Arsenic and Cancer of the Urinary Tract
Authors: Cantor Kenneth P.
Published: July 2002

Inorganic arsenic in drinking water is a recognized cause of cancers of the skin, lung, and bladder. In the absence of an animal model for studying arsenic carcinogenesis, epidemiologic studies provide the only quantitative data for guiding risk assessment at levels that commonly occur in drinking water. To date, most estimates of risk at low and moderate levels of exposure (<200 µg/liter) have been based on extrapolation from ecologic studies of populations exposed to much higher levels. Epidemiologic data from the prospective cohort study by Chiou et al. that appears in this issue of the Journal (Am J Epidemiol 2001;153:411–18) make an important contribution to improving the precision of the estimated risk of transitional cell carcinoma of the urinary tract associated with ingested arsenic from drinking water. The great strength of the study derives from having individually based measures of exposure and cancer diagnoses. Arsenic in water is a topic of great concern and controversy, and epidemiologic studies will continue to provide crucial information about the risks of cancer and other diseases associated with ingested arsenic.
Multivariate Logistic Regression for Familial Aggregation of Two Disorders. I. Development of Models and Methods
Authors: Hudson James I. , Laird Nan M. , Betensky Rebecca A.
Published: July 2002

The question of whether two disorders cluster together, or coaggregate, within families often arises. This paper considers how to analyze familial aggregation of two disorders and presents two multivariate logistic regression methods that model both disorder outcomes simultaneously. The first, a proband predictive model, predicts a relative's outcomes (the presence or absence of each of the two disorders) by using the proband's disorder status. The second, a family predictive model derived from the quadratic exponential model, predicts a family member's outcomes by using all of the remaining family members' disorder statuses. The models are more realistic, flexible, and powerful than univariate models. Methods for estimation and testing account for the correlation of outcomes among family members and can be implemented by using commercial software.
Incidence of Guillain-Barré Syndrome following Infection with Campylobacter jejuni
Authors: McCarthy Noel , Giesecke Johan
Published: July 2002

Evidence of recent or ongoing Campylobacter jejuni infection has been found in approximately one out of every four cases of Guillain-Barré syndrome (GBS). It is increasingly accepted that C. jejuni infection is an important causal factor for GBS. However, the likelihood of GBS' occurring following an episode of C. jejuni gastroenteritis has not been measured. The authors measured the incidence of GBS in a large cohort of persons with laboratory-confirmed C. jejuni infection. Cases of C. jejuni infection were derived from the Swedish national laboratory reporting system for the years 1987–1995. Follow-up for GBS was carried out using the Swedish national hospital inpatient register. Nine cases of GBS were detected in the cohort, which comprised 29,563 cases of C. jejuni infection—a rate of 30.4 per 100,000 (95% confidence interval: 13.9, 57.8). This compares with an expected incidence of 0.3 per 100,000 in a 2-month period in the general population. GBS is an important but rare complication of C. jejuni infection. The risk of developing GBS during the 2 months following a symptomatic episode of C. jejuni infection is approximately 100 times higher than the risk in the general population.
ProbeDesigner: for the design of probesets for branched DNA (bDNA) signal amplification assays.
Authors: Bushnell S , Budde J , Catino T , Cole J , Derti A , Kelso R , Collins M L , Molino G , Sheridan P , Monahan J , Urdea M
Published: July 2002

MOTIVATION: The sensitivity and specificity of branched DNA (bDNA) assays are derived in part through the judicious design of the capture and label extender probes. To minimize non-specific hybridization (NSH) events, which elevate assay background, candidate probes must be computer screened for complementarity with generic sequences present in the assay. RESULTS: We present a software application which allows for rapid and flexible design of bDNA probesets for novel targets. It includes an algorithm for estimating the magnitude of NSH contribution to background, a mechanism for removing probes with elevated contributions, a methodology for the simultaneous design of probesets for multiple targets, and a graphical user interface which guides the user through the design steps. AVAILABILITY: The program is available as a commercial package through the Pharmaceutical Drug Discovery program at Chiron Diagnostics.
Efficient large-scale sequence comparison by locality-sensitive

hashing
Authors: Buhler Jeremy
Published: July 2002

Motivation: Comparison of multimegabase genomic DNA sequences is a popular technique for finding and annotating conserved genome features. Performing such comparisons entails finding many short local alignments between sequences up to tens of megabases in length. To process such long sequences efficiently, existing algorithms find alignments by expanding around short runs of matching bases with no substitutions or other differences. Unfortunately, exact matches that are short enough to occur often in significant alignments also occur frequently by chance in the background sequence. Thus, these algorithms must trade off between efficiency and sensitivity to features without long exact matches.

Results: We introduce a new algorithm, lsh-all-pairs, to find ungapped local alignments in genomic sequence with up to a specified fraction of substitutions. The length and substitution rate of these alignments can be chosen so that they appear frequently in significant similarities yet still remain rare in the background sequence. The algorithm finds ungapped alignments efficiently using a randomized search technique, locality-sensitive hashing. We have found lsh-all-pairsto be both efficient and sensitive for finding local similarities with as little as 63% identity in mammalian genomic sequences up to tens of megabases in length

Availability: Contact the author at the address below.

Contact: jbuhler@cs.washington.edu

Supplementary information: The sequences and local alignment data described in this work are available at http://bio.cs.washington.edu/jbuhler-bioinformatics-2001/.
Tumor classification by partial least squares using microarray
gene expression data
Authors: Nguyen Danh V. , Rocke David M.
Published: July 2002

Motivation: One important application of gene expression microarray data is classification of samples into categories, such as the type of tumor. The use of microarrays allows simultaneous monitoring of thousands of genes expressions per sample. This ability to measure gene expression en masse has resulted in data with the number of variables p(genes) far exceeding the number of samples N. Standard statistical methodologies in classification and prediction do not work well or even at all when N < p. Modification of existing statistical methodologies or development of new methodologies is needed for the analysis of microarray data.

Results: We propose a novel analysis procedure for classifying (predicting) human tumor samples based on microarray gene expressions. This procedure involves dimension reduction using Partial Least Squares (PLS) and classification using Logistic Discrimination (LD) and Quadratic Discriminant Analysis (QDA). We compare PLS to the well known dimension reduction method of Principal Components Analysis (PCA). Under many circumstances PLS proves superior; we illustrate a condition when PCA particularly fails to predict well relative to PLS. The proposed methods were applied to five different microarray data sets involving various human tumor samples: (1) normal versus ovarian tumor; (2) Acute Myeloid Leukemia (AML) versus Acute Lymphoblastic Leukemia (ALL); (3) Diffuse Large B-cell Lymphoma (DLBCLL) versus B-cell Chronic Lymphocytic Leukemia (BCLL); (4) normal versus colon tumor; and (5) Non-Small-Cell-Lung-Carcinoma (NSCLC) versus renal samples. Stability of classification results and methods were further assessed by re-randomization studies.

Availability: The methodology can be implemented using a combination of standard statistical methods, available, for example, in SAS. Illustrative SAS code is available from the first author.

Contact: nguyen@wald.ucdavis.edu; dmrocke@ucdavis.edu

* To whom correspondence should be addressed.
The Rocky Road to Mass Production: Change and Continuity in the U.S. Foundry Industry, 1890–1940
Authors: Harris Howell John
Published: July 2002

This article is a pioneering exploration of technological change in the U.S. foundry industry from the period of its most dramatic growth through its interwar stagnation and decline. Not only does it describe key changes in the mechanization and reorganization of manufacturing processes that helped transform parts of the industry into sites of classic “Fordist” mass production, but it also explains why the impact of these changes was so slow and limited. Through analysis that divides the “foundry industry” into its constituent parts (defined in terms of the forms of business organization and the types of product market that characterized them), the article locates change and continuity within different sectors of an “industry” that was in fact plural rather than singular.
Clinical and economic considerations in the treatment of acute exacerbations of chronic bronchitis
Authors: Destache Christopher J. , Dewan Naresh , O'Donohue Walter J. , Campbell J. Clayton , Angelillo Vito A.
Published: July 2002

Limited data exist to guide physicians in the cost-effective treatment of acute exacerbation of chronic bronchitis (AECB). Therefore, the main objective of this study was to determine the antimicrobial efficacy and related costs for patients with AECB. A retrospective review of 60 outpatient medical records with a diagnosis of chronic obstructive pulmonary disease (COPD) and chronic bronchitis episodes from a pulmonary clinic of a teaching institution was undertaken. The participating patients had a total of 224 episodes of AECB requiring antibiotic treatment. Before review, empirical antibiotic choices were divided into first-line (amoxycillin, co-trimoxazole, tetracyclines, erythromycin), second-line (cephradine, cefuroxime, cefaclor, cefprozil) and third-line (co-amoxiclav, azithromycin, ciprofloxacin) agents. Patients receiving first-line agents failed significantly more frequently than third-line agents (19% vs 7%, P <0.05). Additionally, patients prescribed first-line agents were hospitalized significantly more often for AECB within 2 weeks of outpatient treatment as compared with patients prescribed third-line agents (18.0% vs 5.3% third-line agents; P <0.02). Time between subsequent AECB episodes requiring treatment was significantly longer for patients receiving third-line agents compared with first-line and second-line agents (P <0.005). Pharmacy costs were lowest with first-line agents (first-line US$10.30 ± 8.76; second-line US$24.45 ± 25.65; third-line US$45.40 ± 11.11; P < 0.0001), but third-line agents showed a trend towards lower mean total costs of AECB treatment (first-line US$942 ± 2173; second-line, US$563 ± 2296; third-line, US$542 ± 1946). The use of third-line antimicrobials, co-amoxiclav, ciprofloxacin or azithromycin, significantly reduced the failure rate and need for hospitalization, prolonged the time between AECB episodes, and showed a lower total cost for the management of AECB. Prospective studies are needed to confirm these findings.
The global epidemiology of resistance to ciprofloxacin and the changing nature of antibiotic resistance: a 10 year perspective
Authors: Thomson Christopher J.
Published: July 2002

Many studies have examined the in-vitro activity of ciprofloxacin. The results are for the most part encouraging but we must guard against complacency. Levels of ciprofloxacin resistance vary geographically, while some predictably difficult-to-treat organisms such as Pseudomonas aeruginosa,Staphylococcus aureus and Acinetobacter baumannii present challenges globally. The emergence of resistance in species previously exquisitely sensitive to ciprofloxacin, such as Neisseria gonorrhoeae, in countries associated with ‘ pirate’ production and indiscriminate use of antimicrobials represents a major challenge. Ciprofloxacin continues to show excellent activity againstHaemophilus influenzae and Moraxella catharralis. In general, ciprofloxacin shows good activity against Enterobacteriaceae although the emergence of reduced susceptibility and, sometimes, quinolone resistance in multi-resistant isolates should be noted.
Intron—exon structures of eukaryotic model organisms
Authors: Long Manyuan , Deutsch Michael
Published: July 2002

To investigate the distribution of intron—exon structures of eukaryotic genes, we have constructed a general exon database comprising all available introncontaining genes and exon databases from 10 eukaryotic model organisms: Homo sapiens, Mus musculus, Gallus gallus, Rattus norvegicus, Arabidopsis thaliana, Zea mays, Schizosaccharomyces pombe, Aspergillus, Caenorhabditis elegans and Drosophila . We purged redundant genes to avoid the possible bias brought about by redundancy in the databases. After discarding those questionable introns that do not contain correct splice sites, the final database contained 17 102 introns, 21 019 exons and 2903 independent or quasi-independent genes. On average, a eukaryotic gene contains 3.7 introns per kb protein coding region. The exon distribution peaks around 30–40 residues and most introns are 40–125 nt long. The variable intron—exon structures of the 10 model organisms reveal two interesting statistical phenomena, which cast light on some previous speculations. (i) Genome size seems to be correlated with total intron length per gene. For example, invertebrate introns are smaller than those of human genes, while yeast introns are shorter than invertebrate introns. However, this correlation is weak, suggesting that other factors besides genome size may also affect intron size. (ii) Introns smaller than 50 nt are significantly less frequent than longer introns, possibly resulting from a minimum intron size requirement for intron splicing.
The evolution of cost efficient swimming in marine mammals: limits to energetic optimization
Authors: Williams Terrie M.
Published: July 2002

Mammals re–entered the oceans less than 60 million years ago. The transition from a terrestrial to an aquatic lifestyle required extreme morphological and behavioural modifications concomitant with fundamentally different locomotor mechanisms for moving on land and through water. Energetic transport costs typically reflect such different locomotor modes, but can not be discerned from the fossil record. In this study the energetic challenges associated with changing from terrestrial to aquatic locomotion in primitive marine mammals are examined by comparing the transport, maintenance and locomotor costs of extant mammals varying in degree of aquatic specialization. The results indicate that running and swimming specialists have converged on an energetic optimum for locomotion. An allometric expression, COTTOT= 7.79 mass−0.29(r2= 0.83,n= 6 species), describes the total cost of transport in J kg−1m−1for swimming marine mammals ranging in size from 21 kg to 15,000 kg. This relation is indistinguishable from that describing total transport costs in running mammals. In contrast, the transitional lifestyle of semi–aquatic mammals, similar to that of ancestral marine mammals, incurs costs that are 2.4–5.1 times higher than locomotor specialists. These patterns suggest that primitive marine mammals confronted an energetic hurdle before returning to costs reminiscent of their terrestrial ancestry, and may have reached an evolutionary limit for energetic optimization during swimming.
The role of glial cells in synaptic function
Authors: Bacci Alberto , Verderio Claudia , Pravettoni Elena , Matteoli Michela
Published: July 2002

Glial cells represent the most abundant cell population in the central nervous system and for years they have been thought to provide just structural and trophic support to neurons. Recently, several studies were performed, leading to the identification of an active interaction between glia and neurons. This paper focuses on the role played by glial cells at the level of the synapse, reviewing recent data defining how glia is determinant in synaptogenesis, in the modulation of fully working synaptic contacts and in synaptic plasticity.
Global relationship between anatomical connectivity and activity propagation in the cerebral cortex
Authors: Kotter Rolf , Sommer Friedrich T.
Published: July 2002

Anatomical connectivity is a prerequisite for cooperative interactions between cortical areas, but it has yet to be demonstrated that association fibre networks determine the macroscopical flow of activity in the cerebral cortex. T o test this notion, we constructed a large–scale model of cortical areas whose interconnections were based on published anatomical data from tracing studies. Using this model we simulated the propagation of activity in response to activation of individual cortical areas and compared the resulting topographic activation patterns to electrophysiological observations on the global spread of epileptic activity following intracortical stimulation. Here we show that a neural network with connectivity derived from experimental data reproduces cortical propagation of activity significantly better than networks with different types of neighbourhood–based connectivity or random connections. Our results indicate that association fibres and their relative connection strengths are useful predictors of global topographic activation patterns in the cerebral cortex. This global structure–function relationship may open a door to explicit interpretation of cortical activation data in terms of underlying anatomical connectivity.
Long–wave sensitivity in deep–sea stomiid dragonfish with far–red bioluminescence: evidence for a dietary origin of the chlorophyll–derived retinal photosensitizer of
Malacosteus niger
Authors: Douglas R. H. , Mullineaux C. W. , Partridge J. C.
Published: July 2002

Both residual downwelling sunlight and bioluminescence, which are the two main sources of illumination available in the deep sea, have limited wavebands concentrated around 450–500 nm. Consequently, the wavelengths of maximum absorption (λ
max
) of the vast majority of deep–sea fish visual pigments also cluster in this part of the spectrum. Three genera of deep–sea loose–jawed dragonfish (
Aristostomias
,
Pachystomias
and
Malacosteus
), however, in addition to the blue bioluminescence typical of most deep–sea animals, also produce far–red light (maximum emission 4700 nm) from suborbital photophores. All three genera are sensitive in this part of the spectrum, to which all other animals of the deep sea are blind, potentially affording them a private waveband for illuminating prey and for interspecific communication that is immune from detection by predators and prey. Aristostomias and Pachystomias enhance their long–wave visual sensitivity by the possession of at least three visual pigments that are long–wave shifted (λ
max
values
ca
. 515, 550 and 590 nm) compared with those of other deep–sea fishes.
Malacosteus
, on the other hand, although it does possess two of these red–shifted pigments (λ
max
values
ca.
520 and 540 nm), lacks the most long–wave–sensitive pigments found in the other two genera. However, it further enhances its long–wave sensitivity with a chlorophyll–derived photosensitizer within its outer segments. The fluorescence emission and excitation spectra of this pigment are very similar to spectra obtained from mesopelagic copepods, which are an important component of diet of
Malacosteus
, suggesting a dietary origin for this pigment.
Self–organized instability in complex ecosystems
Authors: Solé Ricard V. , Alonso David , McKane Alan
Published: July 2002

Why are some ecosystems so rich, yet contain so many rare species? High species diversity, together with rarity, is a general trend in neotropical forests and coral reefs. However, the origin of such diversity and the consequences of food web complexity in both species abundances and temporal fluctuations are not well understood. Several regularities are observed in complex, multispecies ecosystems that suggest that these ecologies might be organized close to points of instability. We explore, in greater depth, a recent stochastic model of population dynamics that is shown to reproduce: (i) the scaling law linking species number and connectivity; (ii) the observed distributions of species abundance reported from field studies (showing long tails and thus a predominance of rare species); (iii) the complex fluctuations displayed by natural communities (including chaotic dynamics); and (iv) the species–area relations displayed by rainforest plots. It is conjectured that the conflict between the natural tendency towards higher diversity due to immigration, and the ecosystem level constraints derived from an increasing number of links, leaves the system poised at a critical boundary separating stable from unstable communities, where large fluctuations are expected to occur. We suggest that the patterns displayed by species–rich communities, including rarity, would result from such a spontaneous tendency towards instability.
Mediator function of the human Rad51B–Rad51C complex in Rad51/RPA-catalyzed DNA strand exchange
Authors: Sigurdsson Stefan , Van Komen Stephen , Bussen Wendy , Schild David , Albala Joanna S. , Sung Patrick
Published: July 2002

Five Rad51-like proteins, referred to as Rad51 paralogs, have been described in vertebrates. We show that two of them, Rad51B and Rad51C, are associated in a stable complex. Rad51B–Rad51C complex has ssDNA binding and ssDNA-stimulated ATPase activities. We also examined the functional interaction of Rad51B–Rad51C with Rad51 and RPA. Even though RPA enhances Rad51-catalyzed DNA joint formation via removal of secondary structure in the ssDNA substrate, it can also compete with Rad51 for binding to the substrate, leading to suppressed reaction efficiency. The competition by RPA for substrate binding can be partially alleviated by Rad51B–Rad51C. This recombination mediator function of Rad51B–Rad51C is likely required for the assembly of the Rad51-ssDNA nucleoprotein filament in vivo.
Finding Genes in the C2C12 Osteogenic Pathway by k-Nearest-Neighbor Classification of Expression Data
Authors: Theilhaber Joachim , Connolly Timothy , Roman-Roman Sergio , Bushnell Steven , Jackson Amanda , Call Kathy , Garcia Teresa , Baron Roland
Published: July 2002

A supervised classification scheme for analyzing microarray expression data, based on the k-nearest-neighbor method coupled to noise-reduction filters, has been used to find genes involved in the osteogenic pathway of the mouse C2C12 cell line studied here as a model for in vivo osteogenesis. The scheme uses as input a training set embodying expert biological knowledge, and provides internal estimates of its own misclassification errors, which furthermore enables systematic optimization of the classifier parameters. On the basis of the C2C12-generated expression data set with 34,130 expression profiles across 2 time courses, each comprised of 6 points, and a training set containing known members of the osteogenic, myoblastic, and adipocytic pathways, 176 new genes in addition to 28 originally in the training set are selected as relevant to osteogenesis. For this selection, the estimated sensitivity is 42% and the posterior false-positive rate (fraction of candidates that are spurious) is 12%. The corresponding sensitivity and false-positive rate for detection of myoblastic genes are 9% and 31%, respectively, and only 4% and ∼100%, respectively, for adipocytic genes, in accordance with an experimental design that predominantly stimulated the osteogenic pathway. Validation of this selection is provided by examining expression of the genes in an independent biological assay involving mouse calvaria (skull bone) primary cell cultures, in which a large fraction of the 176 genes are seen to be strongly regulated, as well as by case-by-case analysis of the genes on the basis of expert domain knowledge. The methodology should be generalizable to any situation in which enough a priori biological knowledge exists to define a training set.

[Online supplementary material available atwww.genome.org]
Experimental determination of dosimetry functions of Ir‐192 sources
Authors: Anctil Jean‐Claude , Clark Brenda G. , Arsenault Clément J.
Published: July 2002

Experimental data related to the dosimetric characteristics of Ir‐192 brachytherapy sources are limited. The aim of this work was to obtain the dosimetry functions required by the American Association of Physicists in Medicine Task Group 43 for both a low and a high dose‐rate iridium‐192 brachytherapy source through dose measurements in a water‐equivalent phantom. Dose measurements have been performed using lithium fluoride thermoluminescent detectors positioned in a polystyrene phantom at distances from the source that vary from 1 to 10 cm, with 1 cm intervals, and at angles that vary from 0° to 170° with 10° intervals. The anisotropy functions, radial dose functions, and dose rate constants were determined for both brachytherapy sources. The precision of results obtained on those relatively fine intervals of angles and distances provides clinics with the possibility to use and interpolate the complete data sets for treatment planning.
On the electromagnetic force on a polarizable body
Authors: Engel A. , Friedrichs R.
Published: July 2002

The force on a macroscopic polarizable body in an inhomogenous electromagnetic field is calculated for three simple exactly solvable situations. By comparing different approaches, we pinpoint possible pitfalls and resolve recent confusion about the force density in ferrofluids.
Wave propagation, stress relaxation, and grain-to-grain shearing in saturated, unconsolidated marine sediments
Authors: Buckingham Michael J.
Published: July 2002

A linear theory of wave propagation in saturated, unconsolidated granular materials, including marine sediments, is developed in this article. Since the grains are unbonded, it is assumed that the shear rigidity modulus of the medium is zero, implying the absence of a skeletal elastic frame. The analysis is based on two types of shearing, translational and radial, which occur at grain contacts during the passage of a wave. These shearing processes act as stress-relaxation mechanisms, which tend to return the material to equilibrium after the application of a dynamic strain. The stress arising from shearing is represented as a random stick-slip process, consisting of a random succession of deterministic stress pulses. Each pulse is produced when micro-asperities on opposite surfaces of a contact slide against each other. The quantity relevant to wave propagation is the average stress from all the micro-sliding events, which is shown to be a temporal convolution between the deterministic stress, h(t), from a single event and the probability, q(t), of an event occurring between times t and t+dt. This probability is proportional to the velocity gradient normal to the tangent plane of contact between grains. The pulse shape function, h(t), is derived by treating the micro-sliding as a strain-hardening process, which yields an inverse-fractional-power-law dependence on time. Based on two convolutions, one for the stress relaxation from translational and the other from radial shearing, the Navier–Stokes equation for the granular medium is derived. In a standard way, it is split into two equations representing compressional and shear wave propagation. From these wave equations, algebraic expressions are derived for the wave speeds and attenuations as functions of the porosity and frequency. Both wave speeds exhibit weak, near-logarithmic dispersion, and the attenuations scale essentially as the first power of frequency. A test of the theory shows that it is consistent with wave speed and attenuation data acquired recently from a sandy sediment in the Gulf of Mexico during the SAX99 experiment. If dispersion is neglected, the predicted expressions for the wave speeds reduce to forms which are exactly the same as those in the empirical elastic model of a sediment proposed by Hamilton. On this basis, the concept of a “skeletal elastic frame” is interpreted as an approximate, but not equivalent, representation of the rigidity introduced by grain-to-grain interactions.