bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of Muscle Microvascular Oxygen Pressures: Compartmentalization of Phosphorescent Probe
Authors: POOLE DAVID C. , BEHNKE BRAD J. , McDONOUGH PAUL , McALLISTER RICHARD M. , WILSON DAVID F. 
Published: May 2004

Objective: To determine whether the phosphorescent probe Oxyphor R2 (a palladium porphyrin dendrimer) becomes extravasated within normotensive skeletal muscle, R2 perfusion and washout studies were performed using a perfused rat hindlimb preparation.Methods: Phosphorescence signals were monitored in tibialis anterior muscles after 35 min of R2 blood perfusion and across a subsequent washout period that included vasodilation (sodium nitroprusside, SNP, ∼3 × 10−2 M).Results: Two responses were evident: Group 1 (n = 4)—Inflowing blood pressure and vascular conductance remained stable close to initial values and subsequently a marked vasodilation was evident with SNP (vascular conductance; R2 blood perfusion, 0.096 ± 0.005; washout, pre‐SNP, 0.085 ± 0.005, post‐SNP, 0.110 ± 0.005 mL/min/mmHg, p < .05, for pre‐ vs. post‐SNP). Baseline phosphorescence signals could be monitored up to 99 ± 36 s post‐SNP when the phosphorescence signal disappeared. For these muscles, palladium content was undetectable. Group 2 (n = 3)—Inflowing blood pressure increased 112% and vascular conductance fell ∼ 50%. These hindlimbs were unresponsive to SNP, phosphorescence signal was undiminished by washout and SNP, and muscles became edematous.Conclusions: These results suggest that in normotensive muscle (i.e., Group 1 above), extravasation of phosphorescent probe R2 over 35 min of perfusion is insufficient to yield a detectable phosphorescence signal in skeletal muscle.
Retention of Albumin in the Circulation is Governed by Saturable Renal Cell‐Mediated Processes
Authors: KOLTUN MARIA , COMPER WAYNE D. 
Published: May 2004

Objective: To examine the role of renal processing in the turnover of circulating albumin in the model of reversible overload proteinuria. Specifically, this study determines whether proteinuria due to hyperalbuminemia may be attributed to saturation of renal cell processing of albumin or alterations in diffusive/convective transport of albumin across the glomerular capillary wall.Methods: Overload proteinuria was induced in male Wistar rats by daily intraperitoneal injections of 1.5 g bovine serum albumin (BSA; endotoxin free) for 3 days. Plasma concentration and urinary excretion of total protein and rat serum albumin (RSA) were determined by the biuret assay and radioimmunoassay, respectively. Glomerular size selectivity was assessed by examining the fractional clearance (FC) of neutral [3H]Ficoll using a short‐term, steady‐state approach. Cellular processing was examined by size exclusion chromatography analysis of urinary [14C]albumin and [14C]transferrin structural integrity.Results: Total protein excretion (n = 4–15) increased 7‐fold in BSA‐treated rats (58 ± 26 mg/24 h at baseline vs. 417 ± 259 mg/24 h at day 3), while intact RSA excretion (n = 4–6) increased 200‐fold (0.27 ± 0.15 mg/24 h vs. 53 ± 26 mg/24 h) despite a significant decrease in its plasma concentration. Total protein and albumin excretion returned to basal levels by day 7 (82 ± 16 mg/24 h and 0.93 ± 0.42 mg/24 h, respectively). FC of [3H]Ficoll of equivalent size to albumin did not change in BSA‐treated rats as compared to vehicle controls. Tubular lysosomal processing of proteins was altered at peak proteinuria, as determined by changes in the structural integrity of urinary [14C]albumin, as well as [14C]transferrin, but returned to normal by day 7.Conclusions: This study demonstrates the lack of proportionality between changes in plasma concentration and urinary excretion of albumin, as well as the lack of change in the glomerular size selectivity to albumin. The profound but reversible changes in the amount and integrity of excreted protein suggest that cell‐mediated processes are saturated by albumin concentrations, leading to the development of proteinuria in this model.
Differential Expression of E‐ and P‐Selectin in the Microvasculature of Sickle Cell Transgenic Mice
Authors: Wood Katherine , Russell Janice , Hebbel Robert P. , Granger D. Neil 
Published: May 2004

Objective:There is a growing body of evidence that endothelial cells assume an inflammatory phenotype in sickle cell disease. The authors determined whether (1) the expression of E‐ and P‐selectin differs between sickle cell transgenic (βS) mice and their wild‐type counterparts, and (2) blood platelets and/or neutrophils contribute to the altered selectin expression.Methods:Expression of E‐ and P‐selectin was measured in different regional vascular beds of wild‐type and βSmice (with or without thrombocytopenia or neutropenia) using the dual radiolabeled monoclonal antibody technique.Results:Constitutive expression of P‐selectin was significantly increased in the heart, lungs, small bowel, large bowel, and penis of βSversus WT mice. While thrombocytopenia reduced P‐selectin expression in the small bowel and penis of βSmice, neutropenia was associated with a reduction in P‐selectin expression only in the penis. E‐selectin expression was not significantly elevated in any vascular bed except the penis of βSmice.Conclusions:Sickle cell disease promotes an increased P‐selectin expression in several vascular beds. An accumulation of platelets may explain the increased P‐selectin expression observed in some vascular beds.
An Adenovirus‐Mediated Gene‐Transfer Model of Angiogenesis in Rat Mesentery
Authors: WANG WEN‐YING , WHITTLES CHERYL E. , HARPER STEVEN J. , BATES DAVID O. 
Published: May 2004

Objective: To develop an adenovirus‐mediated angiogenesis model, dependent on VEGF, in a system amenable to functional characterization.Methods: Adenovirus (AdV) expressing VEGF (Ad‐VEGF) or GFP (Ad‐EGFP) (1–3.3 × 108 TCID50/mL), and Monastral blue were injected into the fat pad on either side of a mesenteric connective tissue panel of halothane‐anesthetized male Wistar rats after intravital microscopic imaging. The intestine was replaced in the animal, the laparotomy was sutured, and the animal was allowed to recover. Six days later, the same connective tissue panel was identified from the Monastral blue depot and the mesentery was imaged as before, and then excised, fixed, and stained for endothelial cells (GSL isolectin‐1B4), proliferating cells, VEGF, VEGF‐R2, and actin. The increase in fractional microvascular area (FVA) was measured, and proliferating cell density, sprout density, vessel branch point density, vessel density, and mean vessel length were determined.Results: AdVEGF injection significantly increased the fractional vessel area (2.9 ± 0.4‐fold), proliferating endothelial cell density (1.7 ± 0.1‐fold), sprout density (3.1 ± 0.3‐fold), branch point density (1.9 ± 0.1‐fold), and the microvessel density (1.4 ± 0.1‐fold), and decreased the mean vessel length (0.69 ± 0.04‐fold). VEGF‐R2 staining was evident near sprouting tips of endothelial cells, but not on the tip itself, and evidence for arteriogenesis was observed as well as clear evidence of angiogenesis.Conclusions: Ad‐VEGF injection into the fat pad of the rat induced significant angiogenesis in the mesentery. This two‐dimensional model of VEGF‐induced angiogenesis is amenable to physiological, biochemical, and molecular assessment and may be a useful tool to help understand mechanisms of angiogenesis.
Acetylcholine‐Induced Vasodilation and Reactive Hyperemia Are Not Affected by Acute Cyclo‐Oxygenase Inhibition in Human Skin
Authors: Dalle‐Ave Anne , Kubli Sandrine , Golay Sandrine , Delachaux Anne , Liaudet Lucas , Waeber Bernard , FEIHL FRANÇOIS 
Published: May 2004

Objective:To examine whether prostaglandins are involved in endothelium‐dependent vasodilatory responses of the skin microcirculation.Methods:Twenty‐three young male volunteers were studied on 2 different days 1–3 weeks apart. On each experimental day the forearm skin blood flow response to iontophoretically applied acetylcholine (Ach, an endothelium‐dependent vasodilator) was determined with laser Doppler imaging following the intravenous administration of either the cyclo‐oxygenase inhibitor lysine acetylsalicylate (L‐AS), 900 mg, or the oral intake of indomethacin, 75 mg. Acetylcholine was iontophoresed both in presence and in absence of surface anesthesia. In some subjects, the effects of L‐AS on skin reactive hyperemia were also assessed.Results:Acute cyclo‐oxygenase inhibition with either drug influenced neither the skin blood flow response to 4 different doses of Ach (0.28, 1.4, 7, and 14 mC/cm2) nor reactive hyperemia. The peak vasodilatory response to Ach was significantly increased by skin anesthesia, regardless of whether the subjects received the cyclo‐oxygenase inhibitor or not. For example, the mean response (± SD) to the largest dose of Ach (tested in 6 subjects, expressed in perfusion units) were as follows: in absence of anesthesia: L‐AS 339 ± 105, placebo 344 ± 68; with anesthesia: L‐AS 453 ± 76, placebo 452 ± 65 (p< .01 for effect of anesthesia).Conclusions:These data give no support for a contribution of prostaglandins to acetylcholine‐induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine‐induced vasodilation via a prostaglandin‐independent mechanism.
Knot signature functions are independent
Authors: Cha Jae , Livingston Charles 
Published: May 2004

A Seifert matrix is a square integral matrix

V
V

satisfying

det
(
V
−

V
T

)
=
±
1.

\begin{equation*}\det (V - V^T) =\pm 1. \end{equation*}

To such a matrix and unit complex number

ω
\omega

there corresponds a signature,

σ
ω

(
V
)
=

sign

(
(
1
−
ω
)
V
+
(
1
−

ω
¯

)

V
T

)
.

\begin{equation*}\sigma _\omega (V) = \mbox {sign}( (1 - \omega )V + (1 - \bar {\omega })V^T). \end{equation*}

Let

S
S

denote the set of unit complex numbers with positive imaginary part. We show that

{

σ
ω

}

ω
∈
S

\{\sigma _\omega \}_ { \omega \in S }

is linearly independent, viewed as a set of functions on the set of all Seifert matrices. If

V
V

is metabolic, then

σ
ω

(
V
)
=
0

\sigma _\omega (V) = 0

unless

ω
\omega

is a root of the Alexander polynomial,

Δ
V

(
t
)
=
det
(
V
−
t

V
T

)

\Delta _V(t) = \det (V - tV^T)

. Let

A
A

denote the set of all unit roots of all Alexander polynomials with positive imaginary part. We show that

{

σ
ω

}

ω
∈
A

\{\sigma _\omega \}_ { \omega \in A }

is linearly independent when viewed as a set of functions on the set of all metabolic Seifert matrices. To each knot

K
⊂

S
3

K \subset S^3

one can associate a Seifert matrix

V
K

V_K

, and

σ
ω

(

V
K

)

\sigma _\omega (V_K)

induces a knot invariant. Topological applications of our results include a proof that the set of functions

{

σ
ω

}

ω
∈
S

\{\sigma _\omega \}_ { \omega \in S }

is linearly independent on the set of all knots and that the set of two–sided averaged signature functions,

{

σ
ω
∗

}

ω
∈
S

\{\sigma ^*_\omega \}_ { \omega \in S }

, forms a linearly independent set of homomorphisms on the knot concordance group. Also, if

ν
∈
S

\nu \in S

is the root of some Alexander polynomial, then there is a slice knot

K
K

whose signature function

σ
ω

(
K
)

\sigma _\omega (K)

is nontrivial only at

ω
=
ν

\omega = \nu

and

ω
=

ν
¯

\omega = \overline {\nu }

. We demonstrate that the results extend to the higher-dimensional setting.
The linear heat equation with highly oscillating potential
Authors: Kombe Ismail 
Published: May 2004

In this paper we consider the following initial value problem:\[{∂u∂t=−Hu+V(x)uamp;in RN×(0,T),u(x,0)=u0(x)≥0amp;on RN×{t=0},\begin {cases} \frac {\partial u}{\partial t}=-Hu+V(x)u & \text {in $\mathbb {R}^N\times (0,T)$},\\ u(x,0) = u_0 (x)\geq 0 & \text {on $\mathbb {R}^N \times \{t=0\}$}, \end {cases}\]whereH=−Δ−β|x|2sin⁡(1|x|α)H=-\Delta -\frac {\beta }{|x|^2}\sin (\frac {1}{|x|^{\alpha }})and0≤V∈Lloc1(RN)0\le V\in L_{\text {loc}}^1(\mathbb {R}^N). Nonexistence of positive solutions is analyzed.
Birational morphisms of the plane
Authors: Shpilrain Vladimir , Yu Jie-Tai 
Published: May 2004

Let

A
2

A^2

be the affine plane over a field

K
K

of characteristic

0
0

. Birational morphisms of

A
2

A^2

are mappings

A
2

→

A
2

A^2 \to A^2

given by polynomial mappings

φ
\varphi

of the polynomial algebra

K
[
x
,
y
]

K[x,y]

such that for the quotient fields, one has

K
(
φ
(
x
)
,
φ
(
y
)
)
=
K
(
x
,
y
)

K(\varphi (x), \varphi (y)) = K(x,y)

. Polynomial automorphisms are obvious examples of such mappings. Another obvious example is the mapping

τ
x

\tau _x

given by

x
→
x
,

y
→
x
y

x \to x, ~y \to xy

. For a while, it was an open question whether every birational morphism is a product of polynomial automorphisms and copies of

τ
x

\tau _x

. This question was answered in the negative by P. Russell (in an informal communication). In this paper, we give a simple combinatorial solution of the same problem. More importantly, our method yields an algorithm for deciding whether a given birational morphism can be factored that way.
A dynamically growing self-organizing tree (DGSOT) for hierarchical clustering gene expression profiles
Authors: Luo Feng , Khan Latifur , Bastani Farokh , Yen I-Ling , Zhou Jizhong 
Published: May 2004

Abstract
Motivation: The increasing use of microarray technologies is generating large amounts of data that must be processed in order to extract useful and rational fundamental patterns of gene expression. Hierarchical clustering technology is one method used to analyze gene expression data, but traditional hierarchical clustering algorithms suffer from several drawbacks (e.g. fixed topology structure; mis-clustered data which cannot be reevaluated). In this paper, we introduce a new hierarchical clustering algorithm that overcomes some of these drawbacks.
Result: We propose a new tree-structure self-organizing neural network, called dynamically growing self-organizing tree (DGSOT) algorithm for hierarchical clustering. The DGSOT constructs a hierarchy from top to bottom by division. At each hierarchical level, the DGSOT optimizes the number of clusters, from which the proper hierarchical structure of the underlying dataset can be found. In addition, we propose a new cluster validation criterion based on the geometric property of the Voronoi partition of the dataset in order to find the proper number of clusters at each hierarchical level. This criterion uses the Minimum Spanning Tree (MST) concept of graph theory and is computationally inexpensive for large datasets. A K-level up distribution (KLD) mechanism, which increases the scope of data distribution in the hierarchy construction, was used to improve the clustering accuracy. The KLD mechanism allows the data misclustered in the early stages to be reevaluated at a later stage and increases the accuracy of the final clustering result. The clustering result of the DGSOT is easily displayed as a dendrogram for visualization. Based on a yeast cell cycle microarray expression dataset, we found that our algorithm extracts gene expression patterns at different levels. Furthermore, the biological functionality enrichment in the clusters is considerably high and the hierarchical structure of the clusters is more reasonable.
Availability: DGSOT is available upon request from the authors.
TargetDB: a target registration database for structural genomics projects
Authors: Chen Li , Oughtred Rose , Berman Helen M. , Westbrook John 
Published: May 2004

Abstract
Summary: TargetDB is a centralized target registration database that includes protein target data from the NIH structural genomics centers and a number of international sites. TargetDB, which is hosted by the Protein Data Bank (RCSB PDB), provides status information on target sequences and tracks their progress through the various stages of protein production and structure determination. A simple search form permits queries based on contributing site, target ID, protein name, sequence, status and other data. The progress of individual targets or entire structural genomics projects may be tracked over time, and target data from all contributing centers may also be downloaded in the XML format.
Availability: TagetDB is available at http://targetdb.pdb.org/
Heterogeneity detector: finding heterogeneous positions in Phred/Phrap assemblies
Authors: Lee W. H. , Vega V. B. 
Published: May 2004

Abstract
Summary: A modification to Phred and program to detect heterogeneous positions, which is particularly useful in the identification of mutations and other abnormalities in Phred/Phrap genome assemblies.
Availability: The package is made available at http://giscompute.gis.a-star.edu.sg/~charlie/DHetero.html
SWAPSC: sliding window analysis procedure to detect selective constraints
Authors: Fares Mario A. 
Published: May 2004

Abstract
Summary: Sliding-window analysis procedure to detect selective constraints (SWAPSC) is a software system to dissect the constraints on the evolution of protein-coding genes. The program estimates rates of nucleotide substitutions at specific codon regions in each branch of a phylogenetic tree. The program uses several sets of simulated sequence alignments to estimate the probability of synonymous and non-synonymous nucleotide substitutions. Thereafter, a statistical analysis is conducted to determine the optimum window size to detect selective constraints. Finally, the optimum window size is slid along the real alignment and a test for significance of the estimated number of synonymous and non-synonymous nucleotide substitutions in each sliding step is conducted. A number of friendly useful output files is generated.
Availability: SWAPSC is available at http//www.may.ie/academic/biology/staff/mfmolecevolandbioinf.shtml. Distribution versions for both Linux and Windows operating systems are available, including manual and example files.
Hypoxia induces macrophage inflammatory protein‐2 (MIP‐2) gene expression in murine macrophages via NF‐κB: the prominent role of p42/ p44 and PI3 kinase pathways
Authors: Zampetaki A. , Mitsialis S. A. , Pfeilschifter J. , Kourembanas S. 
Published: May 2004

ABSTRACTWe have previously reported that hypoxia induces a pronounced inflammatory response in the mouse lung associated with elevated levels of specific chemokines. To further explore the mechanisms involved in lung inflammation, we exposed RAW 264.7 cells as well as mouse primary macrophages to hypoxia and analyzed chemokine gene expression. Among the genes examined, macrophage inflammatory protein‐2 (MIP‐2) expression was prominently induced by hypoxia both at the mRNA and the protein level. When RAW 264.7 cells were transfected with a panel of plasmids harboring a luciferase marker gene under the control of wild‐type or mutant variants of the MIP‐2 gene promoter, a strong hypoxic induction of expression (9‐ to 17‐fold) was observed. This induction was abolished by a mutation targeted to an NF‐κB binding site in the MIP‐2 promoter. Concordantly, specific NF‐κB binding to the cognate sequence was enriched in nuclear extracts from hypoxic but not normoxic RAW 264.7 cells. The mechanism of MIP‐2 gene induction by hypoxia was further characterized using inhibitors of signaling kinases. Inhibition of the p42/p44 and PI3 kinases but not p38 MAPK abolished the NF‐κB‐driven upregulation of MIP‐2 gene expression by hypoxia. This attenuation of the NF‐κB response to hypoxia did not involve decreased nuclear NF‐κB abundance but correlated with diminished transactivation potential of the p65 subunit. Our results indicate that the hypoxic signal for induction of MIP‐2 gene expression is implemented through enhanced NF‐κB activity and transmitted along the p42/44 and PI3 kinase pathways.
Estrogen and neuroprotection: higher constitutive expression of glutaredoxin in female mice offers protection against MPTP‐mediated neurodegeneration
Authors: Kenchappa Rajappa S. , Diwakar Latha , Annepu Jayasree , Ravindranath Vijayalakshmi 
Published: May 2004

ABSTRACTIncidence of Parkinson's disease is lower in women as compared with men. Although neuroprotective effect of estrogen is recognized, the underlying molecular mechanisms are unclear. MPTP (1‐methyl‐4‐phenyl‐1, 2, 3, 6, tetrahydro‐pyridine), a neurotoxin that causes Parkinson's disease‐like symptoms acts through inhibition of mitochondrial complex I. Administration of MPTP to male mice results in loss of dopaminergic neurons in substantia nigra, whereas female mice are unaffected. Oxidation of critical thiol groups by MPTP disrupts mitochondrial complex I, and up‐regulation of glutaredoxin (a thiol disulfide oxidoreductase) is essential for recovery of complex I. Early events following MPTP exposure, such as increased AP1 transcription, loss of glutathione, and up‐regulation of glutaredoxin mRNA is seen only in male mice, indicating that early response to neurotoxic insult does not occur in females. Pretreatment of female mice with ICI 182,780, estrogen receptor (ER) antagonist sensitizes them to MPTP‐mediated complex I dysfunction. Constitutive expression of glutaredoxin is significantly higher in female mice as compared with males. ICI 182,780 down‐regulates glutaredoxin activity in female mouse brain regions (midbrain and striatum), indicating that glutaredoxin expression is regulated through estrogen receptor signaling. Higher constitutive expression of glutaredoxin could potentially contribute to the neuroprotection seen in female mouse following exposure to neurotoxins, such as MPTP.
Hepatitis B viral HBx induces matrix metalloproteinase‐9 gene expression through activation of ERKs and PI‐3K/AKT pathways: Involvement of invasive potential
Authors: Chung Tae‐Wook , Lee Young‐Choon , Kim Cheorl‐Ho 
Published: May 2004

ABSTRACTHepatitis B virus (HBV) X protein (HBx) has been shown to be essential for the development of hepatocellular carcinoma (HCC). Recently, we have found that HBx causes the progression of liver cancer through down‐expression of PTEN, known as a tumor suppressor gene (1). The prognosis for HCC depends mainly on the clinicopathological characteristic regarding invasion and metastasis. The expression of matrix metalloproteinase (MMP)‐9 has been implicated as playing an important role in HCC invasion and metastasis. We previously reported that HBV infection increased the invasiveness of hepatocytes and HCC cells through the transcriptional activation of MMP‐9 (2). The HBx was shown to activate the mitogen‐activated protein (MAP) kinase and phosphatidylinositol 3‐kinase (PI‐3K) signal cascade, which is essential for activation of transcription factors such as activating protein (AP)‐1 and nuclear factor (NF)‐κB. In this study, we show that the HBx protein stimulates the activities of the PI‐3K‐Akt/ protein kinase B (PKB) as well as extracellular signal‐regulated kinase 1/2 (ERK 1/2) in HBx‐transfected cells. Furthermore, we have shown that enhanced expression of MMP‐9 in HBx‐transfected cells mediated by not only activation of AP‐1 transcriptional activity through ERKs pathway but also activation of NF‐κB transcriptional activity through PI‐3K‐AKT/PKB pathway, and was associated with the invasive potential. However, treatment with U0126 (known as the ERKs inhibitor) or wortmannin (known as the PI‐3K inhibitor), but not SB203580 (known as the p38 MAPK inhibitor), markedly inhibited the expression of MMP‐9 induced by HBx in HBx‐ transfected cells. Seemingly, the invasiveness of HBx‐transfected cells was decreased by treating with U0126 or wortmannin, but not SB203580. These results clearly suggest that the HBx contributed to the transcriptional regulation of MMP‐9 through the ERKs and PI‐3K‐AKT/PKB pathway, and increased an invasive potential of cells.