bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tie2 activation contributes to hemangiogenic regeneration after myelosuppression
Authors: Kopp Hans-Georg , Avecilla Scott T. , Hooper Andrea T. , Shmelkov Sergey V. , Ramos Carlos A. , Zhang Fan , Rafii Shahin 
Published: April 2005

Abstract
Chemotherapy- or radiation-induced myelosuppression results in apoptosis of cycling hematopoietic cells and induces regression of bone marrow (BM) sinusoidal vessels. Moreover, timely regeneration of BM neovessels is essential for reconstitution of hematopoiesis. However, the identity of angiogenic factors that support reconstitution of BM's vasculature is unknown. Here, we demonstrate that angiopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 (Tie2) signaling contributes to the assembly and remodeling of BM neovessels after myelosuppression. Using transgenic mice where the Tie2 promoter drives the reporter LacZ gene (Tie2-LacZ), we demonstrate that at steady state, there was minimal expression of Tie2 in the BM vasculature. However, after 5-fluorouracil (5-FU) treatment, there was a rapid increase in plasma vascular endothelial growth factor A (VEGF-A) levels and expansion of Tie2-positive neovessels. Inhibition of Tie2 resulted in impaired neoangiogenesis, leading to a delay in hematopoietic recovery. Conversely, angiopoietin-1 (Ang-1) stimulated hematopoiesis both in wild-type and thrombopoietin-deficient mice. In addition, Ang-1 shortened the duration of chemotherapy-induced neutropenia in wild-type mice. Exogenous VEGF-A and Ang-1 stimulated Tie2 expression in the BM vasculature. These data suggest that VEGF-A–induced up-regulation of Tie2 expression on the regenerating vasculature after BM suppression supports the assembly of sinusoidal endothelial cells, thereby promoting reconstitution of hematopoiesis. Angiopoietins may be clinically useful to accelerate hemangiogenic recovery after myelosuppression.
Beyond the Evidence of the New Hypertension Guidelines. Blood pressure measurement – is it good enough for accurate diagnosis of hypertension? Time might be in, for a paradigm shift (I)
Authors: Pater Cornel 
Published: April 2005

Abstract
Despite widespread availability of a large body of evidence in the area of hypertension, the translation of that evidence into viable recommendations aimed at improving the quality of health care is very difficult, sometimes to the point of questionable acceptability and overall credibility of the guidelines advocating those recommendations.
The scientific community world-wide and especially professionals interested in the topic of hypertension are witnessing currently an unprecedented debate over the issue of appropriateness of using different drugs/drug classes for the treatment of hypertension. An endless supply of recent and less recent "drug-news", some in support of, others against the current guidelines, justifying the use of selected types of drug treatment or criticising other, are coming out in the scientific literature on an almost weekly basis. The latest of such debate (at the time of writing this paper) pertains the safety profile of ARBs vs ACE inhibitors.
To great extent, the factual situation has been fuelled by the new hypertension guidelines (different for USA, Europe, New Zeeland and UK) through, apparently small inconsistencies and conflicting messages, that might have generated substantial and perpetuating confusion among both prescribing physicians and their patients, regardless of their country of origin.
The overwhelming message conveyed by most guidelines and opinion leaders is the widespread use of diuretics as first-line agents in all patients with blood pressure above a certain cut-off level and the increasingly aggressive approach towards diagnosis and treatment of hypertension. This, apparently well-justified, logical and easily comprehensible message is unfortunately miss-obeyed by most physicians, on both parts of the Atlantic.
Amazingly, the message assumes a universal simplicity of both diagnosis and treatment of hypertension, while ignoring several hypertension-specific variables, commonly known to have high level of complexity, such as:
- accuracy of recorded blood pressure and the great inter-observer variability,
- diversity in the competency and training of diagnosing physician,
- individual patient/disease profile with highly subjective preferences,
- difficulty in reaching consensus among opinion leaders,
- pharmaceutical industry's influence, and, nonetheless,
- the large variability in the efficacy and safety of the antihypertensive drugs.
The present 2-series article attempts to identify and review possible causes that might have, at least in part, generated the current healthcare anachronism (I); to highlight the current trend to account for the uncertainties related to the fixed blood pressure cut-off point and the possible solutions to improve accuracy of diagnosis and treatment of hypertension (II).
HDBStat!: A platform-independent software suite for statistical analysis of high dimensional biology data
Authors: Trivedi Prinal , Edwards Jode W , Wang Jelai , Gadbury Gary L , Srinivasasainagendra Vinodh , Zakharkin Stanislav O , Kim Kyoungmi , Mehta Tapan , Brand Jacob PL , Patki Amit , Page Grier P , Allison David B 
Published: April 2005

Abstract
Background
Many efforts in microarray data analysis are focused on providing tools and methods for the qualitative analysis of microarray data. HDBStat! (High-Dimensional Biology-Statistics) is a software package designed for analysis of high dimensional biology data such as microarray data. It was initially developed for the analysis of microarray gene expression data, but it can also be used for some applications in proteomics and other aspects of genomics. HDBStat! provides statisticians and biologists a flexible and easy-to-use interface to analyze complex microarray data using a variety of methods for data preprocessing, quality control analysis and hypothesis testing.

Results
Results generated from data preprocessing methods, quality control analysis and hypothesis testing methods are output in the form of Excel CSV tables, graphs and an Html report summarizing data analysis.

Conclusion
HDBStat! is a platform-independent software that is freely available to academic institutions and non-profit organizations. It can be downloaded from our website http://www.soph.uab.edu/ssg_content.asp?id=1164.
Workflows in bioinformatics: meta-analysis and prototype implementation of a workflow generator
Authors: Garcia Castro Alexander , Thoraval Samuel , Garcia Leyla J , Ragan Mark A 
Published: April 2005

Abstract
Background
Computational methods for problem solving need to interleave information access and algorithm execution in a problem-specific workflow. The structures of these workflows are defined by a scaffold of syntactic, semantic and algebraic objects capable of representing them. Despite the proliferation of GUIs (Graphic User Interfaces) in bioinformatics, only some of them provide workflow capabilities; surprisingly, no meta-analysis of workflow operators and components in bioinformatics has been reported.

Results
We present a set of syntactic components and algebraic operators capable of representing analytical workflows in bioinformatics. Iteration, recursion, the use of conditional statements, and management of suspend/resume tasks have traditionally been implemented on an ad hoc basis and hard-coded; by having these operators properly defined it is possible to use and parameterize them as generic re-usable components. To illustrate how these operations can be orchestrated, we present GPIPE, a prototype graphic pipeline generator for PISE that allows the definition of a pipeline, parameterization of its component methods, and storage of metadata in XML formats. This implementation goes beyond the macro capacities currently in PISE. As the entire analysis protocol is defined in XML, a complete bioinformatic experiment (linked sets of methods, parameters and results) can be reproduced or shared among users. Availability:http://if-web1.imb.uq.edu.au/Pise/5.a/gpipe.html (interactive), ftp://ftp.pasteur.fr/pub/GenSoft/unix/misc/Pise/ (download).

Conclusion
From our meta-analysis we have identified syntactic structures and algebraic operators common to many workflows in bioinformatics. The workflow components and algebraic operators can be assimilated into re-usable software components. GPIPE, a prototype implementation of this framework, provides a GUI builder to facilitate the generation of workflows and integration of heterogeneous analytical tools.
Focusing in bioproduction science
Authors: Villaverde Antonio 
Published: April 2005

Abstract
As in other Biotechnological fields, the microbial production of recombinant proteins and other biomolecules can be approached from multiple angles through the help of diverse technologies of increasing complexity. To better reach all the specialized niches in bioproduction, Microbial Cell Factories is now inviting authors to prepare concise Reviews (eventually miniReviews), covering relevant areas that deserve specific and highly focused attention. By the publication of such contributions, the journal will promote the revision of new insights around the Cell Factory concept in a highly comprehensive way, in molecular, cellular and environmental contexts.
Vertical distribution of zooplankton: density dependence and evidence for an ideal free distribution with costs
Authors: Lampert Winfried 
Published: April 2005

Abstract

Background

In lakes with a deep-water algal maximum, herbivorous zooplankton are faced with a trade-off between high temperature but low food availability in the surface layers and low temperature but sufficient food in deep layers. It has been suggested that zooplankton (Daphnia) faced with this trade-off distribute vertically according to an "Ideal Free Distribution (IFD) with Costs". An experiment has been designed to test the density (competition) dependence of the vertical distribution as this is a basic assumption of IFD theory.

Results

Experiments were performed in large, indoor mesocosms (Plankton Towers) with a temperature gradient of 10°C and a deep-water algal maximum established below the thermocline. As expected, Daphnia aggregated at the interface between the two different habitats when their density was low. The distribution spread asymmetrically towards the algal maximum when the density increased until 80 % of the population dwelled in the cool, food-rich layers at high densities. Small individuals stayed higher in the water column than large ones, which conformed with the model for unequal competitors.

Conclusion

The Daphnia distribution mimics the predictions of an IFD with costs model. This concept is useful for the analysis of zooplankton distributions under a large suite of environmental conditions shaping habitat suitability. Fish predation causing diel vertical migrations can be incorporated as additional costs. This is important as the vertical location of grazing zooplankton in a lake affects phytoplankton production and species composition, i.e. ecosystem function.
CABOB: A Fast Optimal Algorithm for Winner Determination in Combinatorial Auctions
Authors: Sandholm Tuomas , Suri Subhash , Gilpin Andrew , Levine David 
Published: April 2005

Combinatorial auctions where bidders can bid on bundles of items can lead to more economically efficient allocations, but determining the winners is 𝒩𝒫-complete and inapproximable. We present CABOB, a sophisticated optimal search algorithm for the problem. It uses decomposition techniques, upper and lower bounding (also across components), elaborate and dynamically chosen bid-ordering heuristics, and a host of structural observations. CABOB attempts to capture structure in any instance without making assumptions about the instance distribution. Experiments against the fastest prior algorithm, CPLEX 8.0, show that CABOB is often faster, seldom drastically slower, and in many cases drastically faster—especially in cases with structure. CABOB's search runs in linear space and has significantly better anytime performance than CPLEX. We also uncover interesting aspects of the problem itself. First, problems with short bids, which were hard for the first generation of specialized algorithms, are easy. Second, almost all of the CATS distributions are easy, and the run time is virtually unaffected by the number of goods. Third, we test several random restart strategies, showing that they do not help on this problem—the run-time distribution does not have a heavy tail.
The MSOM Society Student Paper Competition: Extended Abstracts of 2004 Winners
Authors: Levi Retsef , Pál Martin , Roundy Robin O. , Shmoys David B. , Subramanian Ravi , Hu Xinxin , Allon Gad , Caro Felipe , Lutze Holly S. 
Published: April 2005

As is our tradition at the journal, we are pleased to publish the extended abstracts from the winners of the 2004 MSOM Student Paper Competition. We do this to celebrate the achievements of these young scholars and provide you with the opportunity to learn about their work in more detail. The 2004 prize committee was chaired by Professor Phil Kaminsky (University of California, Berkeley). The other committee members were: Naren Agrawal (University of Santa Clara), Hyun-Soo Ahn (University of Michigan), Damian Beil (University of Michigan), Fernando Bernstein (Duke University), Izak Duenyas (University of Michigan), Wedad Elmaghraby (Georgia Institute of Technology), Jeremie Gallien (Massachusetts Institute of Technology), Teck Ho (University of Pennsylvania), Seyed Iravani (Northwestern University), Ananth Iyer (Purdue University), Eric Johnson (Dartmouth College), Roman Kapuscinski (University of Michigan), Pinar Keskinocak (Georgia Institute of Technology), Anton Kleywegt (Georgia Institute of Technology), Özalp Özer (Stanford University), Georgia Perakis (Massachusetts Institute of Technology), Alan Scheller-Wolf (Carnegie Mellon University), Sridhar Seshadri (New York University), Max Shen (University of California, Berkeley), David Simchi-Levi (Massachusetts Institute of Technology), Jay Swaminathan (University of North Carolina), Terry Taylor (Columbia University), Beril Toktay (INSEAD), Scott Webster (Syracuse University), and David Wu (Lehigh University).
Differential effects of all-trans-retinoic acid (RA) on Erk1/2 phosphorylation and cAMP accumulation in normal and malignant human prostate epithelial cells: Erk1/2 inhibition restores RA-induced decrease of cell growth in malignant prostate cells
Authors: Pasquali Daniela , Chieffi Paolo , Deery William J , Nicoletti Gianfranco , Bellastella Antonio , Sinisi Antonio A 
Published: April 2005

Objective: All-trans-retinoic acid (RA) regulates cellular growth, differentiation and apoptosis in human prostate by binding to RA receptors. Non-genomic retinoid effects on signal transduction kinases in the cytoplasm are also described in several cells but they are still unknown in prostate cells.
Methods: Using an epithelial cell line derived from normal human prostate (EPN), and normal (NPEC) and malignant (CPEC) epithelial primary cultures of human prostate, we have examined effects of RA on both extracellular signal-regulated kinase 1/2 (Erk1/2) and cAMP accumulation. Then we have verified the effect of the inhibition of Erk1/2 on RA-induced growth arrest and apoptosis in malignant cells.
Results: In NPEC and in EPN treated with RA for up to 24 h, Western blot analyses of Erk1/2 phosphorylation show that RA causes a rapid activation of Erk1/2 within 5 min, which is maintained for 30 min, followed by a return to basal levels. In CPEC, the activated phosphorylation levels persist up to 24 h. While basal cAMP levels are not affected by 30 min treatment with RA in both EPN and NPEC, levels are increased in CPEC. Forskolin-induced cAMP levels are decreased by RA in all cell types. CPEC were incubated for up to 96 h with RA with and without the inhibitor of Erk1/2, UO126. CPEC incubated with RA and UO126 for 72 h showed a significant arrest of cell growth and after 96 h apoptosis in 11% of cells.
Conclusions: We show rapid effects of RA on cytoplasmic messenger pathways in human prostate, and that responses can differ between normal and malignant cells. The inhibition of these pathways could improve the efficiency of RA in prostate cancer growth control.
Norethisterone enanthate has neither a direct effect on the testis nor on the epididymis: a study in adult male cynomolgus monkeys (Macaca fascicularis)
Authors: Junaidi Aris , Luetjens C Marc , Wistuba Joachim , Kamischke Axel , Yeung Ching-Hei , Simoni Manuela , Nieschlag Eberhard 
Published: April 2005

Objective: Norethisterone enanthate (NETE) is evaluated in trials of hormonal male contraception. It has been speculated that progestins may exert their contraceptive effects not only by suppressing gonadotropins but also by direct effects on male organs. NETE was given to monkeys in which endogenous gonadotropin secretion was suppressed by a gonadotropin releasing hormone (GnRH) antagonist, and replaced by human follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). If NETE has a direct effect on spermatogenesis and/or epididymal function, some changes in testicular histology, sperm motility and/or morphology should occur soon after exposure to NETE.Methods: Fifteen adult intact male monkeys were grouped and treated for a 38-day period. Group I received GnRH antagonist, FSH, hCG and NETE while group II received a regime identical to group I without NETE and group III received only NETE and vehicle. Ejaculates, body weight, testicular biopsies and volume, and hormones were evaluated.Results: There was a similar pattern of serum FSH and testosterone in groups I and II. Testicular volume and the proportion of tubuli exhibiting spermatids was significantly decreased in group III. There were no significant differences between group I and group II in any parameters measured. The forward progression of sperm was not affected by NETE treatment. The consistently low percentages of grade c sperm indicated no sign of hyperactivation. No changes in the gross morphology of the acrosome were detected.Conclusions: Short-term NETE treatment has neither a direct effect on the testis nor on the epididymis in this nonhuman primate model and its contraceptive effects appear to be exerted exclusively through gonadotropin suppression.
Sheehan’s syndrome: baseline characteristics and effect of 2 years of growth hormone replacement therapy in 91 patients in KIMS – Pfizer International Metabolic Database
Authors: Keleştimur Fahrettin , Jonsson Peter , Molvalilar Senay , Gomez Jose Manuel , Auernhammer Christoph J , Colak Ramiz , Koltowska-Häggström Maria , Goth Miklos I 
Published: April 2005

Objective: Sheehan’s syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. It is one of the most important causes of hypopituitarism, and hence growth hormone deficiency (GHD), in developing countries. However, little is known about the effects of growth hormone (GH) replacement therapy in patients with Sheehan’s syndrome.
Design: The demographic background characteristics of 91 GH-deficient patients with Sheehan’s syndrome (mean age ± s.d., 46.3 ± 9.4 years) were compared with those of a group of 156 GH-deficient women (mean age ± s.d., 51.5 ± 13.1 years) with a non-functional pituitary adenoma (NFPA). The baseline characteristics and the effects of 2 years of GH replacement therapy were also studied in the 91 patients with Sheehan’s syndrome and an age-matched group of 100 women with NFPA (mean age ± s.d. 44.5 ± 10.2 years).
Results: All patients were enrolled in KIMS (Pfizer International Metabolic Database). Patients with Sheehan’s syndrome were significantly younger at pituitary disorder onset, diagnosis of GHD and at entry into KIMS than patients with NFPA (P < 0.01), and had significantly lower insulin-like growth factor I levels (P < 0.001). At baseline, quality of life (QoL) was significantly (P < 0.05) reduced in patients with Sheehan’s syndrome compared with those with NFPA (P < 0.001). With regard to treatment effects, lean body mass increased significantly (P < 0.05), QoL improved significantly (P < 0.05) and total and low-density lipoprotein-cholesterol decreased significantly (P < 0.05) in patients with Sheehan’s syndrome after 1 year of GH replacement therapy. Similar significant changes in QoL and lipid profiles occurred in patients with NFPA after 2 years of GH replacement. Blood pressure remained unchanged in patients with Sheehan’s syndrome, but decreased significantly (P < 0.01) in the group with NFPA after 1 year, before returning to pretreatment levels at 2 years.
Conclusions: In conclusion, patients with Sheehan’s syndrome have more severe GHD compared with individuals with NFPA. GH replacement therapy in patients with Sheehan’s syndrome may have beneficial effects on QoL, body composition and lipid profile.
The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men
Authors: Haijma Sander V , van Dam P Sytze , de Vries Wouter R , Maitimu-Smeele Inge , Dieguez Carlos , Casanueva Felipe F , Koppeschaar Hans P F 
Published: April 2005

Objective and design: Ageing and obesity result in decreased activity of the GH/IGF-I axis and concomitant impaired GH responses to secretory stimuli. We therefore determined the validity of the GH cut-off value of 15.0 μg/l in the GH-releasing hormone (GHRH)/GH releasing peptide-6 (GHRP-6) test for the diagnosis of GH deficiency in elderly or severely obese men.
Methods: We performed a combined GHRH/GHRP-6 test in ten elderly men (mean age 74 years; mean body mass index (BMI) 24.6 kg/m2), nine obese men (mean age 47 years; mean BMI 40.6 kg/m2) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m2). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100 μg) and GHRP-6 (93 μg) were given intravenously as a bolus injection. Repeated GH measurements were performed for two hours. Results: Both peak GH levels and areas under the curve (AUC) were significantly lower in the obese than in the controls (peak 13.2 vs 53.4 μg/l, P = 0.001; AUC 707 vs 3250 μg/l × 120 min; P = 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0 μg/l; AUC 2274 μg/l × 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0 μg/l associated with severe GH deficiency. All others had GH peak levels exceeding this threshold. IGFBP-3 levels were significantly lower in the elderly than in the controls (1.35 vs 2.05 mg/l, P = 0.001). Baseline GH or IGF-I did not differ significantly between groups.
Conclusions: GH responses following GHRH/GHRP-6 administration were significantly reduced in severely obese men, but were not significantly reduced in elderly men, despite a negative trend. Our data indicate that the cut-off GH level of 15.0 μg/l after GHRH + GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.