bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenofovir Disoproxil Fumarate and an Optimized Background Regimen of Antiretroviral Agents as Salvage Therapy for Pediatric HIV Infection
Authors: Hazra Rohan , Gafni Rachel I. , Maldarelli Frank , Balis Frank M. , Tullio Antonella N. , DeCarlo Ellen , Worrell Carol J. , Steinberg Seth M. , Flaherty John , Yale Kitty , Kearney Brian P. , Zeichner Steven L. 
Published: November 2005

Objectives. Highly active antiretroviral therapy has altered the course of HIV infection among children, but new antiretroviral agents are needed for treatment-experienced children with drug-resistant virus. Tenofovir disoproxil fumarate (DF) is a promising agent for use in pediatric salvage therapy, because of its tolerability, efficacy, and resistance profile. We designed this study to provide preliminary pediatric safety and dosing information on tenofovir DF, while also providing potentially efficacious salvage therapy for heavily treatment-experienced, HIV-infected children.Methods. Tenofovir DF, alone and in combination with optimized background antiretroviral regimens, was studied among 18 HIV-infected children (age range: 8.3–16.2 years) who had progressive disease with ≥2 prior antiretroviral regimens, in a single-center, open-label trial. Tenofovir DF monotherapy for 6 days was followed by the addition of individualized antiretroviral regimens. Subjects were monitored with HIV RNA reverse transcription-polymerase chain reaction, flow cytometry, and routine laboratory studies; monitoring for bone toxicity included measurement of lumbar spine bone mineral density (BMD) with dual-energy x-ray absorptiometry. Subjects were monitored through 48 weeks.Results. Two subjects developed grade 3 elevated hepatic transaminase levels during monotherapy and were removed from the study. The remaining 16 subjects had a median of 4 antiretroviral agents (range: 3–5 agents) added to tenofovir DF. HIV plasma RNA levels decreased from a median pretreatment level of 5.4 log10 copies per mL (range: 4.1–5.9 log10 copies per mL) to 4.21 log10 copies per mL at week 48 (n = 15), with 6 subjects having &lt;400 copies per mL, including 4 with &lt;50 copies per mL. The overall median increases in CD4+ T cell counts were 58 cells per mm3 (range: −64 to 589 cells per mm3) at week 24 and 0 cells per mm3 (range: −274 to 768 cells per mm3) at week 48. The CD4+ cell responses among the virologic responders were high and sustained. The major toxicity attributed to tenofovir DF was a &gt;6% decrease in BMD for 5 of 15 subjects evaluated at week 48, necessitating the discontinuation of tenofovir DF therapy for 2; all 5 subjects experienced &gt;2 log10 copies per mL decreases in HIV plasma RNA levels.Conclusions. Tenofovir DF-containing, individualized, highly active antiretroviral therapy regimens were well tolerated and effective among heavily treatment-experienced, HIV-infected children. Loss of BMD may limit tenofovir DF use among prepubertal patients.
DH‐I‐180‐3‐Mediated Photodynamic Therapy: Biodistribution and Tumor Vascular Damage
Authors: Lim Dae‐Seog , Kol Si‐Hwan , Lee Chang‐Hee , Ahn Woong‐Shick , Lee Won‐Young 
Published: November 2005

ABSTRACTAn important goal of photodynamic therapy (PDT) for treatment of various cancers is to shorten PDT‐performing time and simultaneously enhance PDT efficacy. Here, we investigated the nontumor tissue distribution of and the tumor vascular damage caused by a new photosensitizer, DH‐I‐180–3, in mice with implanted EMT6 mammary tumor cells. In addition, we performed cell‐based assays to evaluate the basic antitumor effect of DH‐I‐180–3PDT in EMT6 cells. After administration of PDT, the type of cell death was characterized to be apoptosis, and a change in the mitochondrial membrane potential was also observed within minutes. On the other hand, tumor growth was remarkably retardedin vivoin mice that received DH‐I‐180–3/PDT, compared with mice in the control group, which were exposed to light irradiation alone. Finally, tumors in some mice nearly healed. The antitumor drug reached a maximum concentration approximately 3 h after administration. However, PDT was most effective when there was substantial accumulation of DH‐I‐180–3 in the tumor vasculature and in healthy tissue. The histological demonstration provided further evidence of tumor vascular damage. On the basis of these findings, we suggest that PDT with the photosensitizer DH‐I‐180–3 induces vascular damage with blood vessel shutdown, in addition to direct killing of tumor cells, in mice.
Intervention in a family of Boolean networks
Authors: Choudhary Ashish , Datta Aniruddha , Bittner Michael L. , Dougherty Edward R. 
Published: November 2005

AbstractMotivation: Intervention in a gene regulatory network is used to avoid undesirable states, such as those associated with a disease. Several types of intervention have been studied in the framework of a probabilistic Boolean network (PBN), which is a collection of Boolean networks in which the gene state vector transitions according to the rules of one of the constituent networks and where network choice is governed by a selection distribution. The theory of automatic control has been applied to find optimal strategies for manipulating external control variables that affect the transition probabilities to desirably affect dynamic evolution over a finite time horizon. In this paper we treat a case in which we lack the governing probability structure for Boolean network selection, so we simply have a family of Boolean networks, but where these networks possess a common attractor structure. This corresponds to the situation in which network construction is treated as an ill-posed inverse problem in which there are many Boolean networks created from the data under the constraint that they all possess attractor structures matching the data states, which are assumed to arise from sampling the steady state of the real biological network.Results: Given a family of Boolean networks possessing a common attractor structure composed of singleton attractors, a control algorithm is derived by minimizing a composite finite-horizon cost function that is a weighted average over all the individual networks, the idea being that we desire a control policy that on average suits the networks because these are viewed as equivalent relative to the data. The weighting for each network at any time point is taken to be proportional to the instantaneous estimated probability of that network being the underlying network governing the state transition. The results are applied to a family of Boolean networks derived from gene-expression data collected in a study of metastatic melanoma, the intent being to devise a control strategy that reduces the WNT5A gene's action in affecting biological regulation.Availability: The software is available on request.Contact: edward@ee.tamu.eduSupplementary information: The supplementary Information is available at
Functional Genomic Analysis of theAUXIN/INDOLE-3-ACETIC ACIDGene Family Members inArabidopsis thaliana [W]
Authors: Overvoorde Paul J. , Okushima Yoko , Alonso José M. , Chan April , Chang Charlie , Ecker Joseph R. , Hughes Beth , Liu Amy , Onodera Courtney , Quach Hong , Smith Alison , Yu Guixia , Theologis Athanasios 
Published: November 2005

AbstractAuxin regulates various aspects of plant growth and development. The AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) genes encode short-lived transcriptional repressors that are targeted by the TRANSPORT INHIBITOR RESPONSE1/AUXIN RECEPTOR F-BOX proteins. The Aux/IAA proteins regulate auxin-mediated gene expression by interacting with members of the AUXIN RESPONSE FACTOR protein family. Aux/IAA function is poorly understood; herein, we report the identification and characterization of insertion mutants in 12 of the 29 Aux/IAA family members. The mutants show no visible developmental defects compared with the wild type. Double or triple mutants of closely related Aux/IAA genes, such as iaa8-1 iaa9-1 or iaa5-1 iaa6-1 iaa19-1, also exhibit wild-type phenotypes. Global gene expression analysis reveals that the molecular phenotypes of auxin-treated and untreated light-grown seedlings are unaffected in the iaa17-6 and iaa5-1 iaa6-1 iaa19-1 mutants. By contrast, similar analysis with the gain-of-function axr3-1/iaa17-1 mutant seedlings reveals dramatic changes in basal and auxin-induced gene expression compared with the wild type. Expression of several type-A ARABIDOPSIS RESPONSE REGULATOR genes and a number of genes involved in cell wall biosynthesis and degradation is repressed in axr3-1/iaa17-1. The data suggest extensive functional redundancy among Aux/IAA gene family members and that enhanced stability of the AXR3/IAA17 protein severely alters the molecular phenotype, resulting in developmental defects.
Releasing First-World Wealth for Global Mission: What Levers Can be Pulled Today?
Authors: Ross Kenneth 
Published: November 2005

AbstractThere has been a lively debate about whether first-world wealth is a benefit or a handicap to worldwide Christian mission. Nonetheless it remains a matter of concern that formidable obstacles stand in the path of a flow of resources from wealthy countries to support missionary work. Church decline in the West, a new parochialism, a consumerist lifestyle, project orientation, soteriological relativism and more sophisticated models of mission are some of the forces which have acted to reduce Western financial support for cross-cultural mission worldwide. Nonetheless there are levers, both old and new, which can be pulled to revive and consolidate such support. The uncancelled mandate of the Great Commission, the cry for justice for the poor, the appeal of catholicity and mutuality and the potential of local initiative and direct involvement of local church members are some of the levers which can propel renewed support for Christian mission worldwide. Many missionary initiatives will stand or fall depending on how effectively these levers can be pulled.
Decreased expression of cytochrome P450 protein in non-malignant colonic tissue of patients with colonic adenoma
Authors: Bergheim Ina , Bode Christiane , Parlesak Alexandr 
Published: November 2005

AbstractBackgroundCytochrome P450 (CYP) enzymes in epithelial cells lining the alimentary tract play an important role in both the elimination and activation of (pro-)carcinogens. To estimate the role of cytochrome P450 in carcinogenesis of the colon, expression patterns and protein levels of four representative CYPs (CYP2C, CYP2E1, CYP3A4 and CYP3A5) were determined in colon mucosa of normal and adenomatous colonic tissue of patients with adenomas and disease-free controls.MethodsExpression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 in colon mucosa of normal and adenomatous colonic tissue of patients with adenoma and disease-free controls was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot.ResultsWith the exception of CYP3A5, expression of CYP mRNA was similar among groups and tissues (e.g. normal colon mucosa and adenoma). CYP3A5 mRNA expression was significantly higher in adenoma in comparison to normal tissue of patients with adenoma (~48%). When comparing protein concentrations of CYPs measured in adenomas with neighboring normal colonic mucosa no differences were found. However, in normal tissue of patients with adenomas, protein levels of CYP2C8, CYP3A4 and CYP3A5, but not that of CYP2E1, were significantly lower than in biopsies obtained from disease-free controls. Specifically, in normal colonic mucosa of patients protein concentrations of CYP2C8, CYP3A4, and CYP3A5 were ~86%, ~69%, and ~54%, respectively, lower than in disease-free controls.ConclusionIn conclusion, among other factors, the altered protein levels of certain CYPs (e.g. CYP2C8, CYP3A4 and CYP3A5) in colon mucosa might contribute to the development of neoplasia in the colon.
Increased risk of cancer among relatives of patients with lung cancer in China
Authors: Jin Yongtang , Xu Yingchun , Xu Ming , Xue Saoli 
Published: November 2005

Abstract

Background
Genetic factors were considered as one of the risk factors for lung cancer or other cancers. The aim of this work was to determine whether a genetic predisposition accounts for such familial aggregation of cancer among relatives of lung cancer probands.

Methods
A case-control study was conducted in 800 case families identified by lung cancer patients (probands), and in 800 control families identified by the probands'spouses. The data were analysed with logistic regression analysis model.

Results
The data revealed a significantly greater overall risk of cancer (OR = 1.82, P < 0.01) in the proband group. The relatives of lung cancer probands maintained an increased risk of non-lung cancer (P < 0.05) after adjusting for confounder factors. The crude odds ratio of a proband family having one family member with cancer was 1.67 compared with control families. Proband families were 2.56 times more likely to have two other family members with cancer. For three cancers and four or more cancers, the risk increased to 3.50 and 5.91, respectively. The most striking differences in cancer prevalence between proband and control families were noted for cancer risk among female relatives. The strongest effects were for not only lung cancer in any female relatives (OR 2.17, 95%CI 1.60–3.64) and mothers (OR 2.78, 95%CI 1.23–5.12) and sisters (OR 2.03, 95%CI 1.26–3.97), but also non-lung cancer in females and mothers (OR 2.00, 95%CI 1.26–3.01, and OR 2.34, 95%CI 1.28–4.40, respectively).

Conclusion
These data support the hypothesis of a genetic susceptibility to cancer in families with lung cancer, and the female genetic susceptibility to cancer might be greater than male.
Biochemical characterization of the Arctic char (Salvelinus alpinus) ovarian progestin membrane receptor
Authors: Berg A Håkan , Thomas Peter , Olsson Per-Erik 
Published: November 2005

Abstract
Membrane progestin receptors are involved in oocyte maturation in teleosts. However, the maturation-inducing steroid (MIS) does not appear to be conserved among species and several progestins may fulfill this function. So far, complete biochemical characterization has only been performed on a few species. In the present study we have characterized the membrane progestin receptor in Arctic char (Salvelinus alpinus) and show that the 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) receptor also binds several xenobiotics, thus rendering oocyte maturation sensitive to environmental pollutants. We identified a single class of high affinity (Kd, 13.8 ± 1.1 nM), low capacity (Bmax, 1.6 ± 0.6 pmol/g ovary) binding sites by saturation and Scatchard analyses. Receptor binding displayed rapid association and dissociation kinetics typical of steroid membrane receptors, with t1/2 s of less than 1 minute. The 17,20beta-P binding also displayed tissue specificity with high, saturable, and specific 17,20beta-P binding detected in ovaries, heart and gills while no specific binding was observed in muscle, brain or liver. Changes in 17,20beta-P binding during oocyte maturation were consistent with its identity as the oocyte MIS membrane receptor. Incubation of fully-grown ovarian follicles with gonadotropin induced oocyte maturation, which was accompanied by a five-fold increase in 17,20beta-P receptor binding. In addition, competition studies with a variety of steroids revealed that receptor binding is highly specific for 17,20beta-P, the likely maturation-inducing steroid (MIS) in Arctic char. The relative-binding affinities of all the other progestogens and steroids tested were less than 5% of that of 17,20beta-P for the receptor. Several ortho, para derivatives of DDT also showed weak binding affinity for the 17,20beta-P receptor supporting the hypothesis that xenobiotics may bind steroid receptors on the oocyte's surface and might thereby interfere with oocyte growth and maturation.
Supply-demand balance in outward-directed networks and Kleiber's law
Authors: Painter Page R 
Published: November 2005

Abstract

Background
Recent theories have attempted to derive the value of the exponent α in the allometric formula for scaling of basal metabolic rate from the properties of distribution network models for arteries and capillaries. It has recently been stated that a basic theorem relating the sum of nutrient currents to the specific nutrient uptake rate, together with a relationship claimed to be required in order to match nutrient supply to nutrient demand in 3-dimensional outward-directed networks, leads to Kleiber's law (b = 3/4).

Methods
The validity of the supply-demand matching principle and the assumptions required to prove the basic theorem are assessed. The supply-demand principle is evaluated by examining the supply term and the demand term in outward-directed lattice models of nutrient and water distribution systems and by applying the principle to fractal-like models of mammalian arterial systems.

Results
Application of the supply-demand principle to bifurcating fractal-like networks that are outward-directed does not predict 3/4-power scaling, and evaluation of water distribution system models shows that the matching principle does not match supply to demand in such systems. Furthermore, proof of the basic theorem is shown to require that the covariance of nutrient uptake and current path length is 0, an assumption unlikely to be true in mammalian arterial systems.

Conclusion
The supply-demand matching principle does not lead to a satisfactory explanation for the approximately 3/4-power scaling of mammalian basal metabolic rate.
Cloud‐resolving model simulations of multiply‐banded frontal clouds
Authors: Pizzamei M. , Gray S. L. , Browning K. A. 
Published: November 2005

AbstractAn idealized two‐dimensional cloud‐resolving model is used to investigate the formation and temporal evolution of multiply‐banded clouds in frontal zones. Radar observations often show both upright and slantwise convection in the circulations associated with such bands. The aim is to examine the interaction between upright and slantwise convection and to determine the mechanisms leading to multiple banding. A warm bubble is used to initiate convection in the frontal zone, which has an initial thermodynamic profile based on observations. Further triggering occurs and banded clouds evolve. The initially upright plumes become tilted due to the so‐called ΔM adjustment process (upscale development). Observed multiple bands in frontal zones are frequently attributed to the release of conditional symmetric instability (CSI). However, in these simulations, there is no evidence of the release of CSI despite the fragmentation of slantwise bands into multiple layers in the mid‐troposphere. Successive triggering of upright convection is instead associated with a spreading cold pool driven by evaporative cooling in the slanted downdraughts. Triggering can occur on both the warm‐ and cold‐air sides of the frontal zone, and is sensitive to the microphysical parametrization used. Copyright © 2005 Royal Meteorological Society.
Impact of antibiotics on pathogens associated with otitis media with effusion
Authors: Hamamoto Yukiko , Gotoh Yukako , Nakajo Yoshimi , Shimoya Satoko , Kayama Chikako , Hasegawa Shingo , Nibu Ken-Ichi 
Published: November 2005

Objective: To further understand the roles of bacteria and antibiotics in the development of otitis media with effusion (OME).Methods: Samples of middle-ear effusion (MEE) were collected during the placement of ventilation tubes to treat chronic OME. Children with acute otitis media within the past three months were excluded from this study. We used polymerase chain reaction (PCR) to detect pathogens and to test the susceptibility of Streptococcus pneumoniae to penicillin.Results: Among MEE samples from 52 children, PCR detected bacterial DNA in 32 per cent (24/75) of them. S. pneumoniae was detected more frequently in middle ears that required ventilation tube insertion at least twice compared with those requiring ventilation tube insertion only once (5/15 versus 4/60; p = 0.013). Higher levels of S. pneumoniae were detected in MEE from children with, than without, a long history of antibiotic administration (7/10 versus 2/14; p = 0.0187). The pbp genes of all isolated S. pneumoniae contained mutations.Conclusions: Long exposure to antibiotics might significantly influence the bacterial genome in MEE.
The Historic Center of Morelia: A Case of Successful Negotiation
Authors: Cabrales Barajas Luis Felipe 
Published: November 2005

The historic center of Morelia is one of the most stately and best conserved in Mexico, so much so that in 1991 it was declared a World Heritage site by UNESCO. Notwithstanding such a mark of distinction, the last 25 years have seen the center invaded by a proliferation of street vendors, a problem that until recently seemed insoluble. It generated not only social and environmental problems but also limited the enjoyment of the public spaces by residents and tourists alike. Thanks to consensual political action and multiple negotiations, the more than 1,500 vendors were removed and relocated in more appropriate locations, leaving the city center to better exhibit its pleasant environment and distinguished architectural past. This paper documents the methods used in the relocation process, especially the role played by the Patronato Pro-Rescate del Centro Hist�rico which, for Mexico, appears most encouraging and has generated a climate of optimism.	El centro hist�rico de Morelia es uno de los m�s se�oriales y mejor conservados de M�xico e incluso en 1991 fue declarado Patrimonio de la Humanidad por parte de la UNESCO. No obstante, la proliferaci�n de comercio informal en las calles y plazas observado durante los �ltimos 25 a�os se convirti� en un problema que parec�a irresoluble y que generaba problemas sociales y ambientales, adem�s de que limitaba el disfrute de los espacios p�blicos, tanto para los ciudadanos locales como para el turismo. Gracias a una labor de consenso pol�tico y de m�ltiples negociaciones se logr� retirar a dichos comerciantes (m�s de 1.500) mismos que fueron realojados en sitios mejor dispuestos con lo cual el centro hist�rico luce una agradable imagen y se encuentra en mejores condiciones para perpetuar su centralidad. Se documentan los mecanismos utilizados y el papel desarrollado por el Patronato Pro-Rescate del Centro Hist�rico para alcanzar este importante objetivo que en M�xico resulta muy alentador y ha generado un clima de optimismo social.