bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for voltage-dependent Cl− permeability in mouse pancreatic β-cells
Authors: Sehlin Janove
Published: February 2005

Microdissected β-cell-rich pancreatic islets from ob/ob-mice were used in studies of transmembrane36Cl− efflux. The mean rate coefficient for36Cl− efflux was stable at 0.158 min−1 during the initial 10 min. Depolarization of the β-cell plasma membrane by acute increases in extracellular K+ (5–130mM) stimulated the36Cl− efflux in a concentration-dependent manner. Glucose-induced (20mM) and K+-induced increases in36Cl− efflux were largely overlapping, but even at 135.9 mM K+, glucose slightly further enhanced the36Cl− efflux rate. The data suggest (1) that pancreatic β-cells are equipped with a voltage-dependent Cl− permeability, (2) that glucose-induced increase in Cl− permeability may, at least partly, be mediated by primary membrane depolarization, and (3) that glucose in addition may activate other mechanisms for β-cell Cl− transport.
Evaluation of in vivo insulin action and glucose metabolism in milk-fed rats
Authors: Kergoat M. , Gespach Ch. , Rosselin G. , Portha B.
Published: February 2005

Milk diet has long been recommended in the management of gastrointestinal pathologies. Since milk feeding represents a high fat-low carbohydrate diet and it is acknowledged that insulin resistance is one of the consequences of high fat feeding, it is important to know whether or not chronic milk feeding leads to an impairment of the insulin-mediated glucose metabolism. To examine this question, adult female rats were given raw cow's milk (50% of total calories as lipids) for 18 days. They were compared to rats raised in parallel and fed the standard laboratory diet (15% of total calories as lipids). At the end of the 18 day period, body weight, daily caloric intake, basal plasma glucose and insulin levels in the milk-fed rats were similar to those in the control rats. In vivo insulin action was assessed with the euglycemichyperinsulinemic clamp technique in anesthetized animals. These studies were coupled with the 2-deoxyglucose technique allowing a measurement of glucose utilization by individual tissues. In the milk fed rats: 1) the basal rate of endogenous glucose production was significantly (p<0.01) reduced (by 20%); 2) their hepatic glucose production was however normally suppressed by hyperinsulinemia; 3) their basal glucose utilization rate was significantly (p<0.01) reduced (by 20%); 4) their glucose utilization rate by the whole-body mass or by individual tissues was normally increased by hyperinsulinemia. These results indicate that insulin action in adult rats is not grossly altered after chronic milk-feeding, at least under the present experimental conditions.
Studies of nucleotides of growth-plate cartilage: evidence linking changes in cellular metabolism with cartilage calcification
Authors: Shapiro Irving M. , Golub Ellis E. , May Mary , Rabinowitz Joseph L.
Published: February 2005

The objective of this study was to examine the nucleotides of chick growth-plate cartilage and to measure the concentration of adenine nucleotides in the pre-mineralizing and mineralizing zones. Nucleotides were isolated from the two regions using a rapid-freezing technique and the concentration of individual components was ascertained by HPLC. The actual values of ATP, ADP, and other nucleotides in cartilage was low. The lowest values were recorded in the mineralized zone. In this latter zone the energy charge ratio and the ATP/ADP ratio were depressed. This was probably due to 02-related inhibition of mitochondrial oxidative activity. Additionally, the percentage of octanoate, a short-chain fatty acid that accumulates when aerobic metabolism is disturbed, was found to have increased in the calcifying zone. These findings suggest that calcification of cartilage is associated with hypoxia-related modulation of chondrocyte metabolism.
Purification of urokinase by monoclonal antibody affinity chromatography
Authors: Hérion P. , Bollen A.
Published: February 2005

Matrix-bound monoclonal antibodies against urokinase have been used to purify this enzyme by affinity chromatography. In a single-step procedure, urokinase can be isolated from crude preparations with high yield and high purity, and without loss of enzymatic activity.
Proteins of guinea-pig bile: selective resorption in the gall bladder
Authors: John W. Garry , Mullock Barbara M. , Hinton Richard H.
Published: February 2005

We have examined and compared the proteins present in guinea-pig bile as collected either from the common hepatic duct or from the gall bladder. Guinea-pig bile, collected from the common bile duct, has a rather low concentration of protein. Detailed examination shows that the concentrations of actively transported proteins such as immunoglobulin A and haptoglobin haemoglobin complexes are markedly lower than in rats although the concentrations of proteins which, like albumin, leak non-specifically into bile are similar in the two species. We also find that the protein composition of guinea-pig bile is extensively and selectively modified by resorp-tion of protein in the gall bladder.
The history of proton-driven ATP formation
Authors: Williams R. J. P.
Published: February 2005

This article sets down the beginnings of some thoughts in bio-energetics. It illustrates how difficult it is in science as elsewhere to know how a new idea is generated. The literature needs very careful examination and separation from personalities.
Interaction of sporidesmin, a mycotoxin from Pithomyces chartarum, with lipid bilayers
Authors: Upreti G. C. , Jain M. K.
Published: February 2005

Sporidesmin, a mycotoxin from Pithomyces chartarum is a hydrophobic molecule. It can therefore be easily incorporated in the cell membrane, where it is likely to cause changes in the bilayer organization and the properties of membrane proteins. In order to understand the redox behaviour of sporidesmin in a hydrophobic environment, we have investigated the effects of oxidized and reduced sporidesmin on the phase transition properties of bilayers and on the susceptibility of bilayers to pancreatic phospholipase A2 (PLA2). The changes induced by sporidesmin in the thermotropic phase transition profiles of dimyristoyl-sn-3-phosphatidyl choline (DMPC) bilayers were similar to those caused by solutes known to localize in the glycerol-backbone region of the lipid bilayer, suggesting a similar localization for oxidized and reduced sporidesmin. Neither form of toxin disrupt the bilayer or membrane organization even at relatively high mole fractions. At concentrations <10 mole% both forms partitioned equally well in the gel and liquid-crystalline phases, whereas at higher concentrations (≈30 mole%) reduced sporidesmin is preferentially localized in the liquid-crystalline phase. These effects of sporidesmin on the phase properties of DMPC vesicles were also reported by the fluorescence behavior of 10-pyrenedecanoic acid (PDA). The effects of oxidized and reduced sporidesmins on PLA2 kinetics are consistent with their ability to perturb bilayer organisation.
δ-Toxin, unlike melittin, has only hemolytic activity and no antimicrobial activity: Rationalization of this specific biological activity
Authors: Dhople Vishnu Mukund , Nagaraj Ramakrishnan
Published: February 2005

The antimicrobial activity of a synthetic peptide corresponding to δ-hemolysin had been examined. The peptide did not exhibit antimicrobial activity against gram negative and gram positive micro-organisms unlike other hemolytic peptides like melittin. This lack of antibacterial activity arises due to the inability of δ-hemolysin to perturb the negatively charged bacterial cell surface and permeabilize the bacterial plasma membrane. However, the red blood cell surface has a structure considerably different from bacteria, and does not act as a barrier to molecules reaching the lipid membrane. Hence δ-toxin can lyse erythrocytes. Thus, the specificity in biological activity has been rationalized in terms of differences, in the interaction of the toxin with the bacterial and red blood cell surfaces.
Chondroitin sulphate at the endothelial lumen of pig aorta: Assay by radiolabelling and by X-ray microanalysis
Authors: Hale G. , Streeter H. B. , Hann A. C. , Gacesa P. , Wusteman F. S.
Published: February 2005

Trypsin-releasable glycosaminoglycans from the luminal surface of intact pig aorta were measured following metabolic labelling with35S]sulphate. Chondroitin sulphate was found to be present at a surface density equal to that already established for heparan sulphate (5×1011 chains per cm2). This result was confirmed by X-ray microanalysis of the luminal sulphur content before and after treatment with specific glycosaminoglycan-degrading enzymes. This result implies that approximately half of the luminal surface is occupied by sulphated glycosaminoglycans.
Sequence analysis of a cDNA clone encoding the C-terminal end of human complement factor H
Authors: Day A. J. , Ripoche J. , Lyons A. , McIntosh B. , Harris T. J. R. , Sim R. B.
Published: February 2005

Peptide sequencing of the complement system regulatory protein, factor H, permitted the synthesis of a mixed sequence oligonucleotide probe. Human liver cDNA libraries were screened and factor H-specific clones selected. No full-length clone was obtained, but the largest available clone, R2a, was found to encode the C-terminal 657 amino acids of factor H. The derived amino acid sequence consists of 10 contiguous internally homologous segments, each about 60 amino acids long. Sequences homologous to these are found in several other complement and non-complement proteins. Such sequences are likely to represent a particular type of tertiary structure subunit.
Semliki Forest virus envelope proteins function as proton channels
Authors: Schlegel Andreas , Omar Adames , Jentsch Pia , Morell Andreas , Kempf Christoph
Published: February 2005

It has been shown that isolated nucleocapsids of Semliki Forest virus (SFV) contract upon low pH exposure (Soederlund et al., 1972). This contraction of the nucleocapsids has been used as an indicator to demonstrate that the spike proteins of SFV can translocate protons into the interior of the virus particle upon low pH (5.8) exposure. Spikeless virus particles obtained after bromelain digestion, which were used as a control, did not translocate protons. This implies that the ectodomain of the spike plays a crucial role for the proton translocation.
Cryptic I antigen activity andMycoplasma pneumoniae-receptor activity associated with sialoglycoprotein GP-2 of bovine erythrocyte membranes
Authors: Feizi T. , Gooi H. C. , Loomes L. M. , Suzuki Y. , Suzuki T. , Matsumoto M.
Published: February 2005

The 250-kDa sialoglycoprotein of bovine erythrocyte membranes, GP-2, has been found to be an exception-ally rich source of branched sialo-oligosaccharides of poly-N-acetyllactosamine (I antigen) type with receptor activity for the human pathogen Mycoplasma pneumoniae. Desialylated GP-2 is the most potent I-active substance thus far tested. Since this gtyco-protein is hydrophobic and can be readily re-incorporated into cell membranes, it should be useful in future studies of the mechanism of production of auto-antibodies to the I antigen which commonly arise following human infection with M. pneumoniae.
Differential expression of the cellular oncogenes c-src and c-yes in embryonal and adult chicken tissues
Authors: Gessler Manfred , Barnekow Angelika
Published: February 2005

The cellular onc- genes c-src and c-yes are expressed very differently during chicken embryonic development. The c-src mRNA and its translational product are detectable at high levels in brain extracts of chicken embryos and adult chickens) whereas muscle extracts show an age-dependent decrease in the amounts of c-src-specific mRNA and pp60c-src kinase activity. In contrast) the levels of c-yes mRNA in brain, heart, and muscle are relatively low in early embryonic stages and increase later on to values comparable to those found for liver) while in adult animals the pattern of c-yes expression is similar to that of the c-src gene. From the close correlation between the levels of pp60c-src its enzymatic activity, and its corresponding mRNA at a given stage of development and in given tissues) it appears that the expression of pp60c-src is primarily controlled at the level of transcription. It is suggested that because of the different patterns of expression) the two cellular oncogenes) c-src and c-yes) play different roles in cell proliferation during early embryonic stages as well as in ensuing differentiation processes.
Quantitation of excretion of dolichol and dolichyl phosphate from the rat
Authors: Connelly Lorraine W. , Keller R. Kennedy
Published: February 2005

In order to gain information on the metabolism of dolichol, the rates of excretion of dolichol and doJichyl phosphate were determined in rats maintained on a dolichol-free diet for 10 days. Analysis of fecal samples collected every 49 h yielded mean output values of 9.0 ± 1,4 and 20.7 ± 3,0 μg/rat/day of dolichot and dolichy] phosphate, respectively. Urinary output rates were 0.56 ± 0.12 and 0.50 ± 0.2g μg/rat/ day of dolichol and dolichyt phosphate, respectively. Thus, excretion is one fate of endogenously synthesized dolichoI compounds in the rat.
Multiplicity in corporate identity strategy
Authors: Leitch Shirley , Motion Judy
Published: February 2005

In this article, van Riel’s theory of common starting points is applied to an organisation in order to further our understanding of the way in which multiplicity may be managed within the corporate identity mix. The article begins by outlining the challenges that postmodern theory has posed for corporate identity theory and the contribution that van Riel’s theory can make to addressing these challenges. The theory of common starting points is then applied to the corporate identity of the Mainfreight corporation.
Composite marginal zone B‐cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases
Authors: Zettl A , Rüdiger T , Marx A , Müller‐Hermelink H K , Ott G
Published: February 2005

Aims : Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B‐cell non‐Hodgkin's lymphoma (B‐NHL). We characterized 12 cases of composite marginal zone B‐cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology.

Methods and results : Eight patients had gastric MZBL of mucosa‐associated lymphoid tissue (MALT)‐type, in five cases with a diffuse large B‐cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT‐type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin‐ and Reed–Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein–Barr virus‐associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT‐type and cHL.

Conclusions : MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT‐type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.
Neuroendocrine differentiation in non‐small cell lung cancer and its relation to prognosis and therapy
Authors: Howe M C , Chapman A , Kerr K , Dougal M , Anderson H , Hasleton P S
Published: February 2005

Aims : Histopathologists report the presence of neuroendocrine (NE) differentiation in non‐small cell lung carcinoma (NSCLC) in up to a third of cases and are often questioned about its clinical relevance. The conclusions of previous studies have been inconsistent. This paper aims to provide an answer by examining a large series together with a comprehensive critique of the literature.

Methods and results : Four hundred and thirty‐nine cases of NSCLC were examined, immunohistochemically, using antibodies to chromogranin A (CGA), synaptophysin (SYN) and CD56/neural cell adhesion molecule (NCAM). Three hundred and forty‐one cases had been treated with surgical resection and the remainder with chemotherapy. The results were compared with clinical outcome. Thity‐six percent of cases had positive staining for at least one NE marker. CGA was positive in 5.5% of cases, SYN in 16.5% and NCAM in 28%. There was no association between the presence of NE markers and survival in either the surgically treated group or the chemotherapy‐treated group. There was also no association between NE markers and response to chemotherapy in the latter group.

Conclusions : The presence of immunohistochemically detected NE differentiation in NSCLC is not of prognostic significance.
Characteristics of submucosal gastric carcinoma with lymph node metastatic disease
Authors: Son H J , Song S Y , Kim S , Noh J H , Sohn T S , Kim D S , Rhee J C
Published: February 2005

Aim : To study the correlation between lymph node metastatic disease and various pathological parameters. Lymph node metastasis is the most important factor in determining the prognosis of patients with early gastric cancer and is significantly associated with the submucosal invasion of neoplastic cells. However, the depth of submucosal layer as well as the depth of submucosal tumour invasion varies among different cases.

Methods and results : We studied various pathological parameters including the macroscopic appearance, location, size, area, differentiation, invasion depth, vascularity and fibrosis of submucosal gastric carcinomas (SMGC), using 248 age‐ and sex‐matched tissue samples. The presence of lymphatic emboli, a larger area, greater size, a non‐flat gross type and an increased vascularity of the tumour were significantly associated with node‐positive SMGC. Among the three depth‐related parameters, the ocular scale measurement, the sm3 method and the sm2 method, only the ocular scale measurement showed a significant correlation with node‐positive SMGC. Using multivariate analysis, the incidence of lymph node metastasis increased in the lymphatic tumour emboli and in the tumours that invaded more than half of the submucosal layer.

Conclusions : These histological indicators seem to be a feasible and easy way to predict lymph node metastatic disease from limited surgery specimens. Pathologists should carefully investigate the lymphatic invasion of tumour cells and measure the invasion depth of the tumour.
HDM2 overexpression and focal loss of p14/ARF expression may deregulate the p53 tumour suppressor pathway in meningeal haemangiopericytomas. Study by double immunofluorescence and laser scanning confocal microscopy
Authors: Martínez J‐C , Palomino J‐C , Cabello A , Sepúlveda J M , De La Cámara A G , Ricoy J‐R
Published: February 2005

Aims : To investigate the p53 pathway in meningeal haemangiopericytomas (MHPCs), p14/ARF, p53 protein expression and two wild‐type (wt) p53‐induced proteins (HDM2 and p21/WAF1) were studied in 18 MHPCs, 11 primary, four of them recurrent on one, one, two and four occasions.

Methods : Immunohistochemical detection of p14/ARF, p53, p21/WAF1, HDM2 and Ki67 proliferative index (PI) protein expression.

Results : Ki67 index was > 5% in eight out 18 cases (44.4%). The PI in recurrent cases increased with neoplastic progression. Simultaneous p53 and wt p53 transactivated gene (p21/WAF, HDM2) expression occurred in all cases. This argues against p53 mutation. HDM2 overexpression was observed in 10 cases (55.5%). Double‐immunofluorescence staining and laser scanning confocal microscopy (LSCM) displayed HDM2 and p53 colocalization. This strongly suggests that HDM2 binds and inactivates p53 that could be pathogenic for MHPCs, by a different mechanism than point mutation. p14/ARF expression > 5% was observed in 12 cases (66.6%). A normal (diffuse) pattern of expression was seen in 13 cases (72.2%). Focal loss of expression was observed in five patients (27.7%): three primary cases and two recurrences. Therefore, p14/ARF down‐regulation may also contribute to the development of MHPC.

Conclusion : HDM2 overexpression, sometimes combined with focal loss of p14/ARF expression, may play a pathogenic role in MHPCs.
PROTEIN SPLICING ELEMENTS AND PLANTS: From Transgene Containment to Protein Purification
Authors: Evans Thomas C. , Xu Ming-Qun , Pradhan Sriharsa
Published: February 2005

Protein splicing the process in which an intein excises itself from a precursor molecule with the concomitant ligation of the flanking protein sequences elements, termed inteins a protein splicing element , have been discovered in all the domains of life. Basic research on inteins has led to a greater understanding of how they mediate the protein splicing process. Because inteins are natural protein engineering elements they have been harnessed for use in a number of applications, including protein purification, protein semisynthesis, and in vivo and in vitro protein modifications. This review focuses on the use of inteins in plants. A split-gene technique utilizes inteins to reconstitute the activity of a transgene product with the goal of limiting the spread of transgenes from a genetically modified plant to a weedy relative. Furthermore, merging the intein tag for protein purification with the large protein yields possible with plants has the potential to produce pharmaceutically important proteins. Finally, relevant techniques that may be used in plants in the future are discussed.
Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart
Authors: Park So-Young , Kim Hyo-Jeong , Wang Shupei , Higashimori Takamasa , Dong Jianying , Kim Yoon-Jung , Cline Gary , Li Hong , Prentki Marc , Shulman Gerald I. , Mitchell Grant A. , Kim Jason K.
Published: February 2005

Insulin resistance in skeletal muscle and heart plays a major role in the development of type 2 diabetes and diabetic heart failure and may be causally associated with altered lipid metabolism. Hormone-sensitive lipase (HSL) is a rate-determining enzyme in the hydrolysis of triglyceride in adipocytes, and HSL-deficient mice have reduced circulating fatty acids and are resistant to diet-induced obesity. To determine the metabolic role of HSL, we examined the changes in tissue-specific insulin action and glucose metabolism in vivo during hyperinsulinemic euglycemic clamps after 3 wk of high-fat or normal chow diet in awake, HSL-deficient (HSL-KO) mice. On normal diet, HSL-KO mice showed a twofold increase in hepatic insulin action but a 40% decrease in insulin-stimulated cardiac glucose uptake compared with wild-type littermates. High-fat feeding caused a similar increase in whole body fat mass in both groups of mice. Insulin-stimulated glucose uptake was reduced by 50–80% in skeletal muscle and heart of wild-type mice after high-fat feeding. In contrast, HSL-KO mice were protected from diet-induced insulin resistance in skeletal muscle and heart, and these effects were associated with reduced intramuscular triglyceride and fatty acyl-CoA levels in the fat-fed HSL-KO mice. Overall, these findings demonstrate the important role of HSL on skeletal muscle, heart, and liver glucose metabolism.
Semiclassical fundamental solutions
Authors: Guidotti Patrick
Published: February 2005

It is the aim of this paper to show how the classical theory, based on fundamental solutions and explicit representations, via special functions can be combined with the functional analytical approach to partial differential equations, to produce semiclassical representation formulae for the solution of equations in cylinder‐like domains.
On the modulus of U‐convexity
Authors: Saejung Satit
Published: February 2005

We prove that the moduli of U‐convexity, introduced by Gao (1995), of the ultrapower of a Banach space X and of X itself coincide whenever X is super‐reflexive. As a consequence, some known results have been proved and improved. More precisely, we prove that uX(1) > 0 implies that both X and the dual space X∗ of X have uniform normal structure and hence the “worth” property in Corollary 7 of Mazcuñán‐Navarro (2003) can be discarded.
Response of Mouse Breast Cancer Cells to Anastrozole, Tamoxifen, and the Combination
Authors: Xanthopoulos J. M. , Romano A. E. , Majumdar S. K.
Published: February 2005

The murine breast cancer cells (4T1) grown both in female BALB/c mice and in culture were treated with anastrozole (50 μg/mL), tamoxifen citrate (5 μg/mL), and the combination of the two drugs in order to determine treatment efficacies, toxic potential, and the mechanism of cell death. The in vivo treatments were evaluated by monitoring tumor growth, development, and life span. The in vitro effects were measured through cell growth kinetics, cell proliferation, mitochondrial membrane potential disruption assay, and light and scanning electron microscopy. All drug treatments extended the mean life span of the 4T1‐inoculated tumor‐bearing mice; however, only tamoxifen and combination treatments statistically increased the life span when compared to untreated mice. Although the most drug inhibitory effect on cell multiplication was observed in the combination treatment, both anastrozole and tamoxifen individually inhibited cell proliferation significantly at most time periods in this mouse breast cancer cell line. The mitochondrial membrane potential disruption assay demonstrated significant increase in the percent of cells undergoing apoptosis in all treatment groups. However, the combination treatment was the most effective in inducing cell death via apoptosis. Light and scanning electron microscopy of the treated cells revealed characteristics such as rounding, clumping, and shrinkage of the cells as well as formation of cell surface blebbing and apoptotic bodies suggestive of cell death via apoptotic pathway.
Impact of Tumor‐Derived CCL2 on Macrophage Effector Function
Authors: Brault M. S. , Kurt R. A.
Published: February 2005

Monocyte chemoattractant protein‐1 (MCP‐1, CCL2) is produced by many different types of cells. In the current investigation, the effect of tumor‐derived CCL2 on macrophages was evaluated to determine the extent to which this chemokine influenced the innate immune response to cancer. To do this, we used the 4T1 murine mammary carcinoma cell line that constitutively expresses CCL2 and generated 4T1 expressing an antisense CCL2 transcript. The antisense‐CCL2‐expressing 4T1 produced no detectable CCL2. Macrophages from female BALB/c mice were exposed to supernatants from these tumor cells. The results showed that tumor‐derived CCL2 was capable of modulating cytokine gene expression but not protein production in resting, activated, and tumor‐associated macrophages. In addition, tumor‐derived CCL2 did not affect phagocytic activity, nitric oxide production, or cytolytic activity of the macrophages. Overall, these data suggest that tumor‐derived CCL2 does not directly influence macrophage‐mediated antitumor activity.
The β3 subunit of the integrin αIIbβ3 regulates αIIb-mediated outside-in signaling
Authors: Liu Junling , Jackson Carl W. , Gruppo Ralph A. , Jennings Lisa K. , Gartner T. Kent
Published: February 2005

Bidirectional signaling is an essential feature of αIIbβ3 function. The αIIb cytoplasmic domain negatively regulates β3-mediated inside-out signaling, but little is known about the regulation of αIIb-mediated outside-in signaling. We show that αIIb-mediated outside-in signaling is enhanced in platelets of a patient lacking the terminal 39 residues of the β3 cytoplasmic tail. This enhanced signaling was detected as thromboxane A2 (TxA2) production and granule secretion, and required ligand cross-linking of αIIbβ3 and platelet aggregation. This outside-in signaling was specifically inhibited by a palmitoylated version of a β3 peptide corresponding to cytoplasmic domain residues R724-R734. Unlike the palmitoylated peptide, the nonpalmitoylated β3 peptide could not cross the platelet membrane and did not inhibit this outside-in signaling. The physiologic relevance of this β3-mediated negative regulation of αIIb outside-in signaling was demonstrated in normal platelets treated with the palmitoylated peptide and a physiologic agonist. Binding of αIIbβ3 complexes to immobilized peptides demonstrated that a peptide corresponding to β3 residues R724-R734 appears to bind to an αIIb cytoplasmic domain peptide containing residues K989-D1002, but not to control peptides. These results demonstrate that αIIb-mediated outside-in signaling resulting in TxA2 production and granule secretion is negatively regulated by a sequence of residues in the membrane distal β3 cytoplasmic domain sequence RKEFAKFEEER.
New approaches for preventing and treating chronic graft-versus-host disease
Authors: Lee Stephanie J.
Published: February 2005

Despite improvements in the practice of allogeneic hematopoietic stem cell transplantation (HCT) over the last 25 years, chronic graft-versus-host disease (GVHD) remains a substantial problem with little change in the incidence, morbidity, and mortality of this complication. In fact, with increased use of peripheral blood, transplantation of older patients, and less immediate transplantation-related mortality, the prevalence of chronic GVHD may increase. One of the difficulties in combating chronic GVHD is a lack of understanding about the pathophysiology of the syndrome. Inherent difficulties in conducting human clinical trials also contribute to the lack of meaningful progress. This review covers potential new approaches to the prevention and treatment of chronic GVHD.
Stability of Data Networks: Stationary and Bursty Models
Authors: Ye Heng-Qing , Ou Jihong , Yuan Xue-Ming
Published: February 2005

This paper studies stability of network models that capture macroscopic features of data communication networks, including the Internet. The network model consists of a set of links and a set of possible routes that are fixed subsets of links. A connection is dynamically established along one of the routes to transmit data as requested and is terminated after the transmission is over. The transmission bandwidth of a link is dynamically allocated, according to specific bandwidth allocation policy, to ongoing connections that traverse the link. A network model is said to be stable under a given bandwidth allocation policy if, roughly, the number of ongoing connections in the network will not blow up over time. We consider a stationary and a bursty network model; the former assumes stochastically stationary arrival processes of connections as did many theoretical studies, while the latter allows more realistic bursty and correlated arrival processes. For both models under a necessary stability condition (i.e., the average offered transmission load on each link is within its bandwidth capacity), we show that the proportionally fair, the minimum potential delay, the max-min fair, and a class of utility-maximizing bandwidth allocation policies ensure network model stability, while some priority-oriented and maximum throughput policies do not. Interestingly, the bandwidth allocation policy that maximizes the arctan(·) utility ensures the stability of the stationary model but not the bursty model. This raises a serious concern about the current practice in the Internet protocol design, since such a policy is thought of as a good approximation of one of the most widely used TCP in the Internet.
An Exact Algorithm for Constrained Two-Dimensional Two-Staged Cutting Problems
Authors: Hifi Mhand , M'Hallah Rym
Published: February 2005

The constrained two-dimensional cutting (C_TDC) problem consists of determining a cutting pattern of a set of n small rectangular piece types on a rectangular stock plate S with length L and width W, to maximize the sum of the profits of the pieces to be cut. Each piece type i, i=1,…,n, is characterized by a length li, a width wi, a profit (or weight) ci, and an upper demand value bi. The upper demand value is the maximum number of pieces of type i that can be cut on S. In this paper, we study the two-staged C_TDC problem, noted C_2TDC. It is a classical variant of the C_TDC where each piece is produced, in the final cutting pattern, by at most two cuts. We solve the C_2TDC problem using an exact algorithm that is mainly based on a bottom-up strategy. We introduce new lower and upper bounds and propose new strategies that eliminate several duplicate patterns. We evaluate the performance of the proposed exact algorithm on problem instances extracted from the literature and compare it to the performance of an existing exact algorithm.
Simulation-Based Booking Limits for Airline Revenue Management
Authors: Bertsimas Dimitris , de Boer Sanne
Published: February 2005

Deterministic mathematical programming models that capture network effects play a predominant role in the theory and practice of airline revenue management. These models do not address important issues like demand uncertainty, nesting, and the dynamic nature of the booking process. Alternatively, the network problem can be broken down into leg-based problems for which there are satisfactory solution methods, but this approach cannot be expected to capture all relevant network aspects. In this paper, we propose a new algorithm that addresses these issues. Starting with any nested booking-limit policy, we combine a stochastic gradient algorithm and approximate dynamic programming ideas to improve the initial booking limits. Preliminary simulation experiments suggest that the proposed algorithm can lead to practically significant revenue enhancements.
Implications of Racial and Gender Differences In Patterns of Adolescent Risk Behavior for HIV And Other Sexually Transmitted Diseases
Authors: Halpern Carolyn Tucker , Hallfors Denise , Bauer Daniel J. , Iritani Bonita , Waller Martha W. , Cho Hyunsan
Published: February 2005

CONTEXT: Sexual and substance use behaviors covary in adolescence. Prevalence of HIV and other sexually transmitted diseases (STDs) differs according to race and gender, yet few studies have systematically investigated risk behavior patterns by subgroup, particularly with nationally representative data.

METHODS: A priori considerations and K‐means cluster analysis were used to group 13,998 non‐Hispanic black and white participants in the National Longitudinal Study of Adolescent Health, Wave 1, according to self‐reported substance use and sexual behavior. Multinomial logit analyses examined racial and gender differences by cluster.

RESULTS: Among 16 clusters, the two defined by the lowest risk behaviors (sexual abstinence and little or no substance use) comprised 47% of adolescents; fewer than 1% in these groups reported ever having received an STD diagnosis. The next largest cluster–characterized by sexual activity (on average, with one lifetime partner) and infrequent substance use–contained 15% of participants but nearly one‐third of adolescent with STDs. Blacks were more likely than whites to be in this group. Black males also were more likely than white males to be in three small clusters characterized by high‐risk sexual behaviors (i.e., having had sex with a male or with at least 14 partners, or for drugs or money). Black females generally were the least likely to be in high‐risk behavior clusters but the most likely to report STDs.

CONCLUSIONS: Adolescents' risk behavior patterns vary by race and gender, and do not necessarily correlate with their STD prevalence. Further investigation of adolescents' partners and sexual networks is needed.
Motion Class Dependency in Observers' Motor Areas Revealed by Functional Magnetic Resonance Imaging
Authors: Sakreida Katrin , Schubotz Ricarda I. , Wolfensteller Uta , von Cramon D. Yves
Published: February 2005

Human and animal data suggest that the mere observation of biological motion activates those premotor areas that also underlie the initiation of the same motion. However, data also indicate that the human premotor cortex (PM), in contrast to the monkey PM, responds not only to the observation of goal-directed (transitive) motion but also to intransitive motion. The present study used functional magnetic resonance imaging to test this hypothesis directly. Participants were presented cycles of intransitive motion specified as belonging to the distal (fingers and mouth), proximal (knee, ankle, elbow, and wrist), or axial (trunk and shoulder) motion class. Attention to motion was behaviorally tested by a forced-choice task on motion acceleration and deceleration. Results revealed extended PM activation for each motion condition. However, direct contrasts showed that the most significant activations were elicited in ventrolateral PM by distal motion, in dorsolateral PM by proximal motion, and medial PM (supplementary motor area) by axial motion. Findings confirm observed intransitive motions to engage premotor areas along a gross-scaled somatotopy.
Linkage evidence of schizophrenia to loci near neuregulin 1 gene on chromosome 8p21 in Taiwanese families
Authors: Liu Chih‐Min , Hwu Hai‐Gwo , Fann Cathy S.J. , Lin Chin‐Yu , Liu Yu‐Li , Ou‐Yang Wen‐Chen , Lee Sandy F‐C
Published: February 2005

Positive linkage of schizophrenia to chromosome 8p22‐21 loci had been reported in the Caucasian samples. This study was designed to replicate this finding by using eleven microsatellite markers on chromosome 8p22‐21 in 52 Taiwanese schizophrenic families with at least two affected siblings. Two phenotype models (narrow: DSM‐IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other non‐affective psychotic disorders) were used to define the disease phenotype. Maximum non‐parametric linkage scores (NPL score) of 2.45 (P = 0.008) and 1.89 (P = 0.02) were obtained for the marker D8S1222 under the broad and narrow models, respectively. Positive linkage was found across about a 4‐cM region. The marker D8S1222 was about 400 kbp distal to the exon 1 of glial growth factor 2 (GGF2), an isoform of Neuregulin 1 gene (NRG1), which has been highly suggested to be a candidate gene for schizophrenia. The results provide suggestive linkage evidence of schizophrenia to loci near NRG1 on chromosome 8p21 in an ethnically distinct Taiwanese sample. Further exploration of the candidate gene and nearby chromosome regions is warranted. © 2005 Wiley‐Liss, Inc.
Model for organizational knowledge creation and strategic use of information
Authors: Heinrichs John H. , Lim Jeen‐Su
Published: February 2005

Nimble competitors competing in a dynamic global marketspace increasingly characterize the current environment faced by many organizations. Providing the organization's knowledge workers with the tools and technology to mine information and generate insights has become a key issue facing organizations. In this study we investigate the potential combined impact of the use of organizational decision models and competitive intelligence tool proficiency on knowledge creation and strategic use of information competence. Regression analysis results show significant main and interaction effects of the organizational decision models and competitive intelligence tool proficiency on four identified factors of knowledge creation and strategic use of information competence: pattern discovery, strategy appraisal, insight generation, and solution formulation. Organizational implications and future research directions are discussed.
Brain activation during semantic judgment of Chinese sentences: A functional MRI study
Authors: Mo Lei , Liu Ho‐Ling , Jin Hua , Yang Ya‐Ling
Published: February 2005

A functional magnetic resonance imaging (fMRI) study was conducted to investigate whether the anatomic substrates of semantic memory may reflect categorical organization and to determine whether the left middle frontal gyrus (Brodmann area [BA] 9) plays a role in Chinese semantic judgment. Unlike previous studies using a word‐retrieval task (e.g., word generation, naming, and word categorization), we used a typical task of semantic knowledge retrieval in cognitive psychology in which subjects were asked to determine whether a sentence describing an attribute of living things or nonliving things was true or not. The experimental conditions evoked extensive activation over several regions of the brain including a very strong activation in the left middle frontal region (BA9 and BA46). Our data show that there is no unique activation associated with living or nonliving things at the statistical threshold used in our study. The results imply that human semantic system is undifferentiated by category at the neural level. Our findings also corroborate and extend the claim that the left middle frontal gyrus plays an important role in reading Chinese at both the sentence and the word level. Hum Brain Mapping 24:305–312, 2005. © 2005 Wiley‐Liss, Inc.
Mutations of the BRAF gene in ulcerative colitis‐related colorectal carcinoma
Authors: Aust Daniela E. , Haase Michael , Dobryden Lyudmyla , Markwarth Annett , Löhrs Udo , Wittekind Christian , Baretton Gustavo B. , Tannapfel Andrea
Published: February 2005

The Raf/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates including growth, proliferation and survival. The BRAF gene is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals. Our study was performed to elucidate a possible function of BRAF in ulcerative colitis (UC)‐related colorectal carcinogenesis. Mutations of BRAF and KRAS were determined in 33 UC‐related colorectal cancers by direct DNA sequencing analyses after microdissection. Mismatch‐repair deficiency was assessed by immunohistochemistry for major mismatch‐repair proteins hMLH1, hMSH2 and hMSH6 and microsatellite analyses of the BAT25 and BAT26 loci. Hypermethylation of the hMLH1 promoter was also tested. The results obtained were correlated with histopathologic variables. Activating BRAF missense mutations were identified in 3/33 UC‐related cancers (9%), 2 of which exhibited a loss of hMLH1‐protein expression and hypermethylation of the hMLH1 promoter. Corresponding nondysplastic UC‐mucosa of these patients did not show BRAF mutations. KRAS mutations were found in 6/33 (18%) UC cancers. All 6 UC cancers with KRAS mutations had an intact BRAF gene as the 3 cancers with BRAF mutations had an intact KRAS gene. There was no significant correlation between BRAF or KRAS status and clinicopathologic variables. Our data indicate that BRAF mutations are not an initiating event in UC‐related carcinogenesis and are associated with mismatch‐repair deficiency through hMLH1‐promoter hypermethylation. Disruption of the Raf/MEK/ERK (MAPK) kinase pathway—either through RAS or BRAF mutation—was detected in 27% of all UC‐related cancers and thus plays an important role in UC‐related carcinogenesis. © 2005 Wiley‐Liss, Inc.
Comparison of 585 and 595 nm laser‐induced vascular response of normal in vivo human skin
Authors: Pikkula Brian M. , Chang David W. , Nelson J. Stuart , Anvari Bahman
Published: February 2005

Background and Objectives

Two wavelengths, 585 and 595 nm, are currently common options for treating vascular malformations such as port‐wine stains (PWS). Controversy exists as to which wavelength induces greater photothermal damage to the blood vessels and subsequent resolution of the malformations.

Study Design/Materials and Methods

We irradiated normal, human skin in vivo at 585 and 595 nm wavelengths using fluences of 10–30 J/cm2 with a 1.5 millisecond laser pulse. The level of purpura, total vascular damage, maximum coagulation depth (MCD), and perivascular damage were quantified by gross observation and histological analysis.

Results

Results demonstrated that 585 nm light caused greater purpura, vascular damage, maximum coagulation depth, and perivascular damage than 595 nm. Purpura showed a positive correlation with total vascular damage to a certain extent beyond which the total vascular damage did not change. For equivalent purpura, 585 and 595 nm produced no statistically significant difference in vascular damage. The difference in the laser‐induced vascular damage between 585 and 595 nm, although statistically significant, was no more than 50%.

Conclusions

The bathochromic (red) shift and formation of met‐hemoglobin, which reduces the 585 nm light absorption and increases that of 595 nm compared to native oxy‐hemoglobin, play a considerable role in creating more parity in vascular damage between the two wavelengths than would be expected based on their respective “native” absorption coefficients alone. Lasers Surg. Med. 36:117–123, 2005. © 2005 Wiley‐Liss, Inc.
Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease
Authors: Saft Carsten , Zange Jochen , Andrich Jürgen , Müller Klaus , Lindenberg Katrin , Landwehrmeyer Bernhard , Vorgerd Matthias , Kraus Peter H. , Przuntek Horst , Schöls Ludger
Published: February 2005

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT‐15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age‐ and gender‐matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD. © 2004 Movement Disorder Society
HIV encephalitis simulating Huntington's disease
Authors: Sevigny Jeffrey J. , Chin Steven S.M. , Milewski Yvonne , Albers Mark W. , Gordon Marc L. , Marder Karen
Published: February 2005

Complications from human immunodeficiency virus (HIV)/acquired immune deficiency syndrome are notorious for mimicking other neurological diseases. We describe a case of HIV encephalitis presenting with the classic clinical features of Huntington's Disease in a woman without known HIV risk factors or other clinical stigmata suggestive of immunosuppression. This case reminds us that HIV should be part of the differential diagnosis in unexplainable neurological diseases. © 2004 Movement Disorder Society
Integration of geometric design and mechanical analysis using B‐spline functions on surface
Authors: Roh Hee Yuel , Cho Maenghyo
Published: February 2005

B‐spline finite element method which integrates geometric design and mechanical analysis of shell structures is presented. To link geometric design and analysis modules completely, the non‐periodic cubic B‐spline functions are used for the description of geometry and for the displacement interpolation function in the formulation of an isoparametric B‐spline finite element. Non‐periodic B‐spline functions satisfy Kronecker delta properties at the boundaries of domain intervals and allow the handling of the boundary conditions in a conventional finite element formulation. In addition, in this interpolation, interior supports such as nodes can be introduced in a conventional finite element formulation. In the formulation of the mechanical analysis of shells, a general tensor‐based shell element with geometrically exact surface representation is employed. In addition, assumed natural strain fields are proposed to alleviate the locking problems. Various numerical examples are provided to assess the performance of the present B‐spline finite element. Copyright © 2005 John Wiley & Sons, Ltd.