bluuebunny/crossref_metadata_2025_split huggingface dataset:
'I Order You to Adapt': Evaluating the Community Policing, French-Style
Authors: Ferret Jérôme 
Published: August 2004

AbstractThis article presents a meta-evaluation of the evaluative researches on the 'police de proximité' led in France over the past twenty years. Five certainties have been highlighted concerning the evaluation of these ambiguous forms of police: the many meanings behind the concept of 'community policing', the danger of a management by the 'numbers' to evaluate a performance, the two meanings of the word 'impact', the problematic idea of 'good practices' in matters of community policing and the misleading idea of the 'resistance to change' in police organisations. Furthermore, the evaluative research on the performance of police organisation will always be dependant two major constitutive doubts: the 'black box' of complex police organisations and the role of politics in the policies of the police. To conclude, we can say that on the one hand a technical form of evaluation exists but, also a politic form of police evaluation is more important in the western states, taking into consideration the 'politisation' of matters of security.
The Implementation and Evaluation of Community Policing in Spain: Results and Future Prospects
Authors: Rabot Audrey 
Published: August 2004

AbstractThis article offers an overview of the implementation and evaluation of community policing programs in Spain today through the analysis of two particularly illustrative practical experiences. The controversial results of the Policía 2000 project – Spain's most consummate nationwide community policing program – pleads for a local imple- mentation of the community policing model. Indeed, as shown by another pioneering reform in Sant Boi de Llobregat (a big town near Barcelona) – which today offers many lessons in matters of evaluation and management of community policing – it is mainly at this level that experiences have been most conclusive.
Telomere dynamics in Fancg-deficient mouse and human cells
Authors: Franco Sonia , van de Vrugt Henri J. , Fernández Piedad , Aracil Miguel , Arwert Fre , Blasco María A. 
Published: August 2004

Abstract
A number of DNA repair proteins also play roles in telomere metabolism. To investigate whether the accelerated telomere shortening reported in Fanconi anemia (FA) hematopoietic cells relates to a direct role of the FA pathway in telomere maintenance, we have analyzed telomere dynamics in Fancg-deficient mouse and human cells. We show here that both hematopoietic (stem and differentiated bone marrow cells, B and T lymphocytes) and nonhematopoietic (germ cells, mouse embryonic fibroblasts [MEFs]) Fancg-/- mouse cells display normal telomere length, normal telomerase activity, and normal chromosome end-capping, even in the presence of extensive clastogen-induced cytogenetic instability (mitomycin C [MMC], gamma-radiation). In addition, telomerase-deficient MEFs with humanlike telomere length and decreased Fancg expression (G5 Terc-/-/Fancg shRNA3 MEFs) display normal telomere maintenance. Finally, early-passage primary fibroblasts from patients with FA of complementation group G as well as primary human cells with reduced FANCG expression (FANCG shRNA IMR90 cells) show no signs of telomere dysfunction. Our observations indicate that accelerated telomere shortening in patients with FA is not due to a role of FANCG at telomeres but instead may be secondary to the disease. These findings suggest that telomerase-based therapies could be useful prophylactic agents in FA aplastic anemia by preserving their telomere reserve in the context of the disease. (Blood. 2004;104:3927-3935)
Lysophosphatidic acid accelerates the development of human mast cells
Authors: Bagga Savita , Price Kursteen S. , Lin Debby A. , Friend Daniel S. , Austen K. Frank , Boyce Joshua A. 
Published: August 2004

AbstractMast cells (MCs) initiate immune responses from mucosal surfaces and perivascular spaces. Stem cell factor (SCF) regulates MC development and viability, but the role of innate serum factors in MC development is unexplored. Cultured cord blood-derived human MCs (hMCs) express mRNA transcripts for all 4 known receptors for lysophosphatidic acid (LPA), an abundant serum-associated lipid growth factor. In an SCF-dependent serum-free culture system, LPA (2.5-10 μM) increased the total number of hMCs by approximately 10-fold compared with cultures maintained in the absence of LPA under otherwise identical conditions. LPA was comitogenic with SCF but did not prolong MC survival. LPA-mediated proliferation was blocked by VPC-32179, a competitive antagonist of LPA1 and LPA3 receptors, and by pertussis toxin, and it was also attenuated by GW9662, a selective antagonist of peroxisome proliferator-activated receptor (PPAR)-γ. LPA accelerated the acquisition of hMC granules and increased Kit expression. hMCs derived in the presence of LPA were functional, as evidenced by their immunoglobulin E (IgE)-dependent histamine release and by their characteristic proliferative responses to interleukin-3 (IL-3), IL-4, and IL-9 in combination with SCF. Thus, LPA acts through LPA receptor and PPAR-γ-dependent pathways to accelerate hMC proliferation and differentiation, and it modulates their phenotype without providing cytoprotection. LPA could facilitate MC hyperplasia in inflammation associated with either innate or adaptive immunity. (Blood. 2004; 104:4080-4087)
Patients with severe sepsis vary markedly in their ability to generate activated protein C
Authors: Liaw Patricia C. Y. , Esmon Charles T. , Kahnamoui Kamyar , Schmidt Shelley , Kahnamoui Sarah , Ferrell Gary , Beaudin Suzanne , Julian Jim A. , Weitz Jeffrey I. , Crowther Mark , Loeb Mark , Cook Deborah 
Published: August 2004

AbstractActivated protein C (APC) supplementation significantly reduces mortality in patients with severe sepsis, presumably by down-regulating coagulation, inflammation, and apoptosis. In vivo, endogenous APC is generated from protein C (PC) “on demand” in response to elevated thrombin levels. Thrombomodulin and endothelial cell protein C receptor are endothelial receptors required to generate APC endogenously. Since these receptors may be down-regulated in sepsis, we measured plasma markers of APC generation in 32 patients with severe sepsis to determine whether APC generation is impaired and whether markers of APC generation correlate with 28-day mortality. Relative to normals, all patients had elevated F1 + 2 and thrombin-antithrombin complex (TAT) levels (markers of thrombin generation and inhibition, respectively), and 28 of 32 patients had reduced PC levels. In 20 patients, APC levels paralleled elevated F1 + 2 levels, whereas 12 patients had low APC levels despite elevated F1 + 2 levels, suggesting that APC generation is impaired in the latter. No significant differences exist between survivors and nonsurvivors with respect to baseline PC levels, F1 + 2 levels, and APACHE II (acute physiology and chronic health evaluation) scores. Baseline APC levels were higher in survivors (P = .024), and baseline F1 + 2/APC ratios were lower in survivors (P = .047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis. (Blood. 2004;104:3958-3964)
Regulation of transferrin receptor 2 protein levels by transferrin
Authors: Robb Aeisha , Wessling-Resnick Marianne 
Published: August 2004

AbstractTransferrin receptor 2 (TfR2) plays a critical role in iron homeostasis because patients carrying disabling mutations in the TFR2 gene suffer from hemochromatosis. In this study, iron-responsive regulation of TfR2 at the protein level was examined in vitro and in vivo. HepG2 cell TfR2 protein levels were up-regulated after exposure to holotransferrin (holoTf) in a time- and dose-responsive manner. ApoTf or high-iron treatment with non–Tf-bound iron failed to elicit similar effects, suggesting that TfR2 regulation reflects interactions of the iron-bound ligand. Hepatic TfR2 protein levels also reflected an adaptive response to changing iron status in vivo. Liver TfR2 protein levels were down- and up-regulated in rats fed an iron-deficient and a high-iron diet, respectively. TfR2 was also up-regulated in Hfe-/- mice, an animal model that displays liver iron loading. In contrast, TfR2 levels were reduced in hypotransferrinemic mice despite liver iron overload, supporting the idea that regulation of the receptor is dependent on Tf. This idea is confirmed by up-regulation of TfR2 in β-thalassemic mice, which, like hypotransferrinemic mice, are anemic and incur iron loading, but have functional Tf. Based on these combined results, we hypothesize that TfR2 acts as a sensor of iron status such that receptor levels reflect Tf saturation.
The α1 helix-β13 strand spanning Leu214 to Val229 of platelet glycoprotein Ibα facilitates the interaction with von Willebrand factor: evidence from characterization of the epitope of monoclonal antibody AP1
Authors: Peng Yuandong , Berndt Michael C. , Cruz Miguel A. , López José A. 
Published: August 2004

AbstractThe glycoprotein Ib-IX-V (GP Ib-IX-V) complex mediates platelet binding to von Willebrand factor (VWF) through its largest polypeptide, GP Ibα. Of the many GP Ibα monoclonal antibodies described, AP1 is of particular interest because it blocks static VWF binding induced by 2 modulators, ristocetin and botrocetin, and platelet adhesion to VWF surfaces under flow. We mapped the AP1 binding site to a region encompassing Arg218 to Tyr228, comprising the α1 helix and β13 strand defined by the GP Ibα crystal structure. AP1 binding absolutely required Arg218, Asp222, and Glu225. We evaluated the ability of cells expressing mutants of this region to bind VWF under static conditions in the presence of modulators, and to attach to and roll on a VWF matrix under flow. These data indicate that 2 regions within the sequence Arg218 to Tyr228 have important roles in VWF binding: the α1 helix has a regulatory role and the β turn and β13 strand bind VWF directly. Despite this, the only effect of a synthetic peptide corresponding to Leu214 to Val229 was to slightly increase the rolling velocity of GP Ibα-expressing Chinese hamster ovary (CHO) cells on VWF. This region thus appears to be more important for maintaining the regional conformation of GP Ibα, thereby facilitating the interaction with VWF. (Blood. 2004;104:3971-3978)
Individualizing therapy – in search of approaches to maximize the benefit of drug treatment (II)
Authors: Pater Cornel 
Published: August 2004

AbstractAdjusting drug therapy to the individual, a common approach in clinical practice, has evolved from 1) dose adjustments based on clinical effects to 2) dose adjustments made in response to drug levels and, more recently, to 3) dose adjustments based on deoxyribonucleic acid (DNA) sequencing of drug-metabolizing enzyme genes, suggesting a slow drug metabolism phenotype. This development dates back to the middle of the 20th century, when several different drugs were administered on the basis of individual plasma concentration measurements. Genetic control of drug metabolism was well established by the 1960s, and pharmakokinetic-based individualized therapy was in use by 1973.
Equivalence and noninferiority trials – are they viable alternatives for registration of new drugs? (III)
Authors: Pater Cornel 
Published: August 2004

AbstractThe scientific community's reliance on active-controlled trials is steadily increasing, as widespread agreement emerges concerning the role of these trials as viable alternatives to placebo trials. These trials present substantial challenges with regard to design and interpretation as their complexity increases, and the potential need for larger sample sizes impacts the cost and time variables of the drug development process. The potential efficacy and safety benefits derived from these trials may never be demonstrated by other methods. Active-controlled trials can develop valuable data to inform both prescribers and patients about the dose- and time-dependent actions of any new drug and can contribute to the management and communication of risks associated with the relevant therapeutic products.
IdentiCS – Identification of coding sequence and in silico reconstruction of the metabolic network directly from unannotated low-coverage bacterial genome sequence
Authors: Sun Jibin , Zeng An-Ping 
Published: August 2004

Abstract
Background
A necessary step for a genome level analysis of the cellular metabolism is the in silico reconstruction of the metabolic network from genome sequences. The available methods are mainly based on the annotation of genome sequences including two successive steps, the prediction of coding sequences (CDS) and their function assignment. The annotation process takes time. The available methods often encounter difficulties when dealing with unfinished error-containing genomic sequence.

Results
In this work a fast method is proposed to use unannotated genome sequence for predicting CDSs and for an in silico reconstruction of metabolic networks. Instead of using predicted genes or CDSs to query public databases, entries from public DNA or protein databases are used as queries to search a local database of the unannotated genome sequence to predict CDSs. Functions are assigned to the predicted CDSs simultaneously. The well-annotated genome of Salmonella typhimurium LT2 is used as an example to demonstrate the applicability of the method. 97.7% of the CDSs in the original annotation are correctly identified. The use of SWISS-PROT-TrEMBL databases resulted in an identification of 98.9% of CDSs that have EC-numbers in the published annotation. Furthermore, two versions of sequences of the bacterium Klebsiella pneumoniae with different genome coverage (3.9 and 7.9 fold, respectively) are examined. The results suggest that a 3.9-fold coverage of the bacterial genome could be sufficiently used for the in silico reconstruction of the metabolic network. Compared to other gene finding methods such as CRITICA our method is more suitable for exploiting sequences of low genome coverage. Based on the new method, a program called IdentiCS (Identi fication of C oding S equences from Unfinished Genome Sequences) is delivered that combines the identification of CDSs with the reconstruction, comparison and visualization of metabolic networks (free to download at http://genome.gbf.de/bioinformatics/index.html).

Conclusions
The reversed querying process and the program IdentiCS allow a fast and adequate prediction protein coding sequences and reconstruction of the potential metabolic network from low coverage genome sequences of bacteria. The new method can accelerate the use of genomic data for studying cellular metabolism.
Disparities in lipid management for African Americans and Caucasians with coronary artery disease: A national cross-sectional study
Authors: Massing Mark W , Foley Kathleen A , Carter-Edwards Lori , Sueta Carla A , Alexander Charles M , Simpson Ross J 
Published: August 2004

Abstract
Background
Individuals with coronary artery disease are at high risk for adverse health outcomes. This risk can be diminished by aggressive lipid management, but adherence to lipid management guidelines is far from ideal and substantial racial disparities in care have been reported. Lipid treatment and goal attainment information is not readily available for large patient populations seen in the fee-for-service setting. As a result, national programs to improve lipid management in this setting may focus on lipid testing as an indicator of lipid management. We describe the detection, treatment, and control of dyslipdemia for African Americans and Caucasians with coronary artery disease to evaluate whether public health programs focusing on lipid testing can eliminate racial disparities in lipid management.

Methods
Physicians and medical practices with high numbers of prescriptions for coronary artery disease medications were invited to participate in the Quality Assurance Program. Medical records were reviewed from a random sample of patients with coronary artery disease seen from 1995 through 1998. Data related to the detection, treatment, and control of dyslipidemia were abstracted from the medical record and evaluated in cross-sectional stratified and logistic regression analyses using generalized estimation equations.

Results
Data from the medical records of 1,046 African Americans and 22,077 Caucasians seen in outpatient medical practices in 23 states were analyzed. African-American patients were younger, more likely to be women and to have diabetes, heart failure, and hypertension. The low density lipoprotein cholesterol (LDL-C) testing rate for Caucasian men was over 1.4 times higher than that for African-American women and about 1.3 times higher than that for African-American men. Almost 60% of tested Caucasian men and less than half of tested African Americans were prescribed lipid-lowering drugs. Tested and treated Caucasian men had the highest LDL-C goal attainment (35%) and African-American men the lowest (21%).

Conclusions
Although increased lipid testing is clearly needed for African Americans, improvements in treatment and control are also necessary to eliminate racial disparities in lipid management. Disparities in treatment and goal attainment must be better understood and reflected in policy to improve the health of underserved populations.
Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder
Authors: Berlant Jeffrey L 
Published: August 2004

Abstract
Background
In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD) observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD.

Methods
Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female) with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5) or augmentation (n = 28). The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C) score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms.

Results
For those taking the PCL-C at both baseline and week 4 (n = 30), total symptoms declined by 49% at week 4 (paired t-test, P < 0.001) with similar subscale reductions for reexperiencing, avoidance/numbing, and hyperarousal symptoms. The response rate at week 4 was 77%. Age, sex, bipolar comorbidity, age at onset of PTSD, duration of symptoms, severity of baseline PCL-C score, and monotherapy versus add-on medication administration did not predict reduction in PTSD symptoms. Median time to full response was 9 days and median dosage was 50 mg/day.

Conclusions
Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.
The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome
Authors: Bouros Demosthenes , Alexandrakis Michael G , Antoniou Katerina M , Agouridakis Panagiotis , Pneumatikos Ioannis , Anevlavis Stavros , Pataka Athanasia , Patlakas George , Karkavitsas Nikolaos , Kyriakou Despina 
Published: August 2004

Abstract
Background
The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS).

Methods
We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C).

Results
An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively).

Conclusions
BALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS.
A faster way to make GFP-based biosensors: Two new transposons for creating multicolored libraries of fluorescent fusion proteins
Authors: Sheridan Douglas L , Hughes Thomas E 
Published: August 2004

Abstract
Background
There are now several ways to generate fluorescent fusion proteins by randomly inserting DNA encoding the Green Fluorescent Protein (GFP) into another protein's coding sequence. These approaches can be used to map regions in a protein that are permissive for GFP insertion or to create novel biosensors. While remarkably useful, the current insertional strategies have two major limitations: (1) they only produce one kind, or color, of fluorescent fusion protein and (2) one half of all GFP insertions within the target coding sequence are in the wrong orientation.

Results
We have overcome these limitations by incorporating two different fluorescent proteins coding sequences in a single transposon, either in tandem or antiparallel. Our initial tests targeted two mammalian integral membrane proteins: the voltage sensitive motor, Prestin, and an ER ligand gated Ca2+ channel (IP3R).

Conclusions
These new designs increase the efficiency of random fusion protein generation in one of two ways: (1) by creating two different fusion proteins from each insertion or (2) by being independent of orientation.