bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteasome-dependent autoregulation of Bruton tyrosine kinase (Btk) promoter via NF-κB
Authors: Yu Liang , Mohamed Abdalla J. , Simonson Oscar E. , Vargas Leonardo , Blomberg K. Emelie M. , Björkstrand Bo , Arteaga H. Jose , Nore Beston F. , Smith C. I. Edvard 
Published: February 2008

AbstractBruton tyrosine kinase (Btk) is critical for B-cell development. Btk regulates a plethora of signaling proteins, among them nuclear factor-[κ]B (NF-κB). Activation of NF-κB is a hallmark of B cells, and NF-κB signaling is severely compromised in Btk deficiency. We here present strong evidence indicating that NF-κB is required for efficient transcription of the Btk gene. First, we found that proteasome blockers and inhibitors of NF-κB signaling suppress Btk transcription and intracellular expression. Similar to Btk, proteasome inhibitors also reduced the expression of other members of this family of kinases, Itk, Bmx, and Tec. Second, 2 functional NF-κB–binding sites were found in the Btk promoter. Moreover, in live mice, by hydrodynamic transfection, we show that bortezomib (a blocker of proteasomes and NF-κB signaling), as well as NF-κB binding sequence-oligonucleotide decoys block Btk transcription. We also demonstrate that Btk induces NF-κB activity in mice. Collectively, we show that Btk uses a positive autoregulatory feedback mechanism to stimulate transcription from its own promoter via NF-κB.
Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis
Authors: Saadoun David , Rosenzwajg Michelle , Landau Dan , Piette Jean Charles , Klatzmann David , Cacoub Patrice 
Published: February 2008

AbstractRituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as mixed cryoglobulinemia (MC). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of peripheral blood B- and T-cell subsets, the clonal VH1–69 cells, as well as the cytokine profile following rituximab therapy. The study involved 21 patients with hepatitis C–related MC who received rituximab, of whom 14 achieved a complete response. Compared with healthy and hepatitis C virus (HCV) controls, pretreatment abnormalities in MC patients included a decreased percentage of naive B cells (P < .05) and CD4+CD25+FoxP3+ regulatory T cells (P = .02) with an increase in memory B cells (P = .03) and plasmablasts (P < .05). These abnormalities were reverted at 12 months after rituximab. Clonal VH1–69+ B cells dramatically decreased following treatment (32% ± 6% versus 8% ± 2%, P = .01). Complete responders of rituximab exhibited an expansion of regulatory T cells (P < .01) accompanied with a decrease in CD8+ T-cell activation (P < .01) and decreased production of interleukin 12 (IL-12; P = .02) and interferon-γ (IFN-γ; P = .01). Our findings indicate that in patients with MC, response to B-cell depletion induced by rituximab effectively normalizes many of the disturbances in peripheral B- and T-lymphocyte homeostasis.
ReAlignerV: Web-based genomic alignment tool with high specificity and robustness estimated by species-specific insertion sequences
Authors: Iwama Hisakazu , Hori Yukio , Matsumoto Kensuke , Murao Koji , Ishida Toshihiko 
Published: February 2008

Abstract

Background
Detecting conserved noncoding sequences (CNSs) across species highlights the functional elements. Alignment procedures combined with computational prediction of transcription factor binding sites (TFBSs) can narrow down key regulatory elements. Repeat masking processes are often performed before alignment to mask insertion sequences such as transposable elements (TEs). However, recently such TEs have been reported to influence the gene regulatory network evolution. Therefore, an alignment approach that is robust to TE insertions is meaningful for finding novel conserved TFBSs in TEs.

Results
We constructed a web server 'ReAlignerV' for complex alignment of genomic sequences. ReAlignerV returns ladder-like schematic alignments that integrate predicted TFBSs and the location of TEs. It also provides pair-wise alignments in which the predicted TFBS sites and their names are shown alongside each sequence. Furthermore, we evaluated false positive aligned sites by focusing on the species-specific TEs (SSTEs), and found that ReAlignerV has a higher specificity and robustness to insertions for sequences having more than 20% TE content, compared to LAGAN, AVID, MAVID and BLASTZ.

Conclusion
ReAlignerV can be applied successfully to TE-insertion-rich sequences without prior repeat masking, and this increases the chances of finding regulatory sequences hidden in TEs, which are important sources of the regulatory network evolution. ReAlignerV can be accessed through and downloaded from http://genet.med.kagawa-u.ac.jp/.
'One patient amongst many': a qualitative analysis of intensive care unit patients' experiences of transferring to the general ward
Authors: Field Kate , Prinjha Suman , Rowan Kathy 
Published: February 2008

Abstract
Introduction
Many patients experience 'relocation stress' when they are transferred from an intensive care unit (ICU) to step-down (high dependency) or general ward care, and much has been written about the psychological causes. This qualitative analysis of in-depth, narrative interviews with former ICU patients explores and examines patients' accounts in order to identify additional causes of relocation stress.

Methods
Forty former ICU patients were recruited throughout the UK, using maximum variation sampling, to achieve a broad range of experiences of intensive care. Interviews in people's homes were recorded on video and audio equipment as part of a study for the Database of Personal Experiences of Health and Illness (DIPEx) web resource. All interviews were transcribed, checked and returned to respondents. For this report, a qualitative thematic analysis was used to explore experiences of transfer.

Results
We found that most people experienced relocation distress not only because of physical and emotional difficulties relating to their illness and treatment and the inevitable anxiety resulting from leaving a protected environment, but also from concrete, practical causes. These included specific concerns about communication, feeding, nursing care and support, as well as ward organization and environment. Written excerpts from the interviews and two video excerpts taken from the DIPEx website illustrate our findings.

Conclusion
We conclude that there are several aspects of care that deserve further examination by researchers and service providers, and that not all of the factors associated with relocation stress should be seen as an inevitable consequence of the psychological adjustment involved in transfer from an ICU.
Early treatment of imported falciparum malaria in the intermediate and intensive care unit setting: an 8-year single-center retrospective study
Authors: Schwake Lukas , Streit Judith Pamela , Edler Lutz , Encke Jens , Stremmel Wolfgang , Junghanss Thomas 
Published: February 2008

AbstractIntroductionImported falciparum malaria is characterized by a broad spectrum of potentially life-threatening complications that may arise even after initiation of appropriate antimalarial drug therapy. Hence, at Heidelberg University Hospital, all patients with newly diagnosed falciparum malaria are initially treated in the intermediate care unit (IMC) or intensive care unit (ICU). The present study was undertaken to evaluate critically the benefit of this strategy, which includes daily consultation with senior specialists in tropical medicine.MethodsWe conducted a retrospective cohort study at the 14-bed combined IMC/ICU of a 1,685-bed university hospital. A cohort of 122 patients with imported falciparum malaria admitted from 1 January 1996 to 31 December 2003 was included.ResultsThirty-four patients (27.9%) developed complications, defined according to the current World Health Organization classification. Most patients (80.3%) studied did not take the recommended chemoprophylaxis against malaria. The majority of patients (89.3% [n = 109]) could be adequately treated in the IMC. Life-threatening complications requiring ICU support occurred in 13 patients (10.7%). All complications were successfully managed. Fifty-five patients (45.1%) fulfilling recently published criteria for outpatient treatment had an excellent therapeutic response and did not require ICU support.ConclusionThis retrospective evaluation demonstrated favourable therapeutic results in hospitalized patients with imported falciparum malaria. Both initial treatment in the medical IMC/ICU and close collaboration between intensivists and specialists in tropical medicine may improve disease outcome among affected patients. Prospective studies are needed to confirm these preliminary findings.
Ex Vivo Simulation of the Action of Antileukemia Drugs by Measuring Apoptosis-Related mRNA in Blood
Authors: Mitsuhashi Masato , Endo Katsuya , Obara Kazuhiko , Izutsu Hiroshi , Ishida Taishi , Chikatsu Norio , Shinagawa Atsushi 
Published: February 2008

Abstract
Background: In conventional bioassays, isolated cells are suspended in culture media, incubated in vitro for several days, and then characterized with respect to any cellular changes. In developing new molecular tests under physiological ex vivo conditions, we quantified the production of mRNAs for p21 and PUMA (p53 up-regulated modulator of apoptosis), which are involved in cell cycle arrest and apoptosis, respectively.
Methods: We stimulated human whole blood with a chemotherapeutic drug (cytarabine, daunorubicin, mitoxantrone, aclarubicin, etoposide, or idarubicin) for 4 h and then quantified mRNA by assessing mRNA recovery and cDNA-synthesis efficiency in each sample. We also used immunoassay and flow cytometry to investigate nucleosome and annexin V, respectively, as apoptosis markers.
Results: Ex vivo mRNA analysis yielded more positive results than nucleosome and annexin V analyses. The concentrations of cytarabine- and daunorubicin-induced p21 and PUMA mRNAs were significantly lower in acute myelogenous leukemia (AML) patients than in healthy controls (P &lt;0.0001), whereas idarubicin induced significantly greater responses in AML patients than in controls (P = 0.01). The patients had different mRNA-response patterns, which were largely classifiable into 4 groups. Prednisone enhanced cytarabine or mitoxantrone induction of p21 and PUMA mRNAs in 3 (2.6%) of 114 reactions. All 15 patients who achieved complete remission had received at least one drug that produced positive mRNA responses, whereas we observed a lack of mRNA response to the clinically used drugs in all 3 cases in which the therapy failed to induce any hematologic improvement.
Conclusion: This study introduced ex vivo mRNA analysis as a candidate platform for drug-sensitivity tests in leukemia.
Epigenetic Marking Prepares the Human HOXA Cluster for Activation During Differentiation of Pluripotent Cells
Authors: Atkinson Stuart P. , Koch Christoph M. , Clelland Gayle K. , Willcox Sarah , Fowler Joanna C. , Stewart Rebecca , Lako Majlinda , Dunham Ian , Armstrong Lyle 
Published: February 2008

Abstract
Activation of Hox gene clusters is an early event in embryonic development since individual members play important roles in patterning of the body axis. Their functions require precise control of spatiotemporal expression to provide positional information for the cells of the developing embryo, and the manner by which this control is achieved has generated considerable interest. The situation is different in pluripotent cells, where HOX genes are not expressed but are held in potentio as bivalent chromatin domains, which are resolved upon differentiation to permit HOX cluster activation. In this study we have used differentiation of the pluripotent embryonal carcinoma cell line NTera2SP12 and the human embryonic stem cell line H9 to examine epigenetic changes that accompany activation of the HOXA cluster and show that specific genomic loci are marked by lysine methylation of histone H3 (H3K4 tri- and dimethyl, H3K9 trimethyl) and acetylation of histone H4 even in the undifferentiated cells. The precise locations of such modified histones may be involved in controlling the colinear expression of genes from the cluster.
Disclosure of potential conflicts of interest is found at the end of this article.
Reciprocal Intraepithelial Interactions Between TP63 and Hedgehog Signaling Regulate Quiescence and Activation of Progenitor Elaboration by Mammary Stem Cells
Authors: Li Na , Singh Samer , Cherukuri Pratima , Li Hua , Yuan Ziqiang , Ellisen Leif W. , Wang Baolin , Robbins David , DiRenzo James 
Published: February 2008

Abstract
TP63 is required for preservation of epithelial regenerative stasis and regulates the activity of diverse genetic pathways; however, specific effector pathways are poorly understood. Data presented here indicate that reciprocal regulatory interactions between hedgehog signaling and TP63 mediate stage-specific effects on proliferation and clonigenicity of separable enriched mammary stem and progenitor fractions. Analysis of ΔN-p63 and TA-p63 indicates segregated expression in mammary stem and progenitor fractions, respectively, demonstrating that differential TP63 promoter selection occurs during elaboration of mammary progenitors by mammary stem cells. This segregation underlies mammary progenitor-specific expression of Indian Hedgehog, identifying it as a binary transcriptional target of TP63. Hedgehog activation in vivo enhances elaboration of mammary progenitors and decreases label retention within mammary stem cell-enriched fractions, suggesting that hedgehog exerts a mitogenic effect on mammary stem cells. Hedgehog signaling promotes differential TP63 promoter usage via disruption of Gli3 or Gli3R accumulation, and shRNA-mediated disruption of Gli3 expression was sufficient to alter TP63 promoter usage and enhance clonigenicity of mammary stem cells. Finally, hedgehog signaling is enhanced during pregnancy, where it contributes to expansion of the mammary progenitor compartment. These studies support a model in which hedgehog activates elaboration and differentiation of mammary progenitors via differential TP63 promoter selection and forfeiture of self-renewing capacity.
Disclosure of potential conflicts of interest is found at the end of this article.
Carboxypeptidase M Expressed by Human Bone Marrow Cells Cleaves the C-Terminal Lysine of Stromal Cell-Derived Factor-1α: Another Player in Hematopoietic Stem/Progenitor Cell Mobilization?
Authors: Marquez-Curtis Leah , Jalili Ali , Deiteren Kathleen , Shirvaikar Neeta , Lambeir Anne-Marie , Janowska-Wieczorek Anna 
Published: February 2008

Abstract
Carboxypeptidase M (CPM) is a membrane-bound zinc-dependent protease that cleaves C-terminal basic residues, such as arginine or lysine, from peptides/proteins. We examined whether CPM is expressed by hematopoietic and stromal cells and could degrade stromal cell-derived factor (SDF)-1α, a potent chemoattractant for hematopoietic stem/progenitor cells (HSPC). We found that (a) CPM transcript is expressed by bone marrow (BM) and mobilized peripheral blood CD34+ cells, myeloid, erythroid, and megakaryocytic cell progenitors, mononuclear cells (MNC), polymorphonuclear cells (PMN), and stromal cells, including mesenchymal stem cells; and that (b) granulocyte-colony-stimulating factor (G-CSF) significantly increases its expression at the gene and protein levels in MNC and PMN. Moreover, we found that recombinant CPM cleaves full-length SDF-1α (1–68) rapidly, removing the C-terminal lysine and yielding des-lys SDF-1α (1–67). We demonstrated that such CPM treatment of SDF-1α reduced the in vitro chemotaxis of HSPC, which, however, was preserved when the CPM was exposed to the carboxypeptidase inhibitor dl-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid. Thus, we present evidence that CPM is expressed by cells occurring in the BM microenvironment and that the mobilizing agent G-CSF strongly upregulates it in MNC and PMN. We suggest that cleavage of the C-terminal lysine residue of SDF-1α by CPM leads to attenuated chemotactic responses and could facilitate G-CSF-induced mobilization of HSPC from BM to peripheral blood.
Disclosure of potential conflicts of interest is found at the end of this article.
A Systematic Methodology for Extrapolating Gas-Oil Ratio During Declining Oil Production
Authors: Lawal Kazeem A. , Uwaga Anthony O. , Osoro Omamoke F. 
Published: February 2008

Abstract
With increasing drive to account for associated gas, it has become necessary to have a reliable technique for extrapolating gas-oil ratio (GOR), commonly used to quantify gas produced with the oil. While there have been significant improvements in the number and quality of techniques available for analysing oil-rate data, GOR prediction has not advanced appreciably. In this paper, a systematic methodology developed on the basis of a new internally consistent GOR model, is presented. Applicability is demonstrated with a field example, which also illustrates its use for estimating recoverable volume of associated gas during oil decline. The good agreement of the results with field data affirms the accuracy of this methodology. While emphasising the importance of consistent data, it is concluded that reservoir and fluid mechanics, as well as operational procedures, are other important considerations when extrapolating GOR. Practical application of this work includes surveillance and management of oil well, reservoir and field.
A Robust Type Curve Solution for Analyzing Pressure-Transient Behaviors of both Vertical and Horizontal Fracture Systems
Authors: Ogunsanya B. O. , Oetama T. P. , Lea J. F. , Heinze L. R. , Adisoemarta P. S. 
Published: February 2008

Abstract
Although there have been many analytical studies on pressure-transient behavior of hydraulic fracture systems, no single analytical solution capable of describing both vertical and horizontal fracture transient state behaviors has been developed. The purpose of this work is to develop a single analytical solution that is robust enough to fit this need.
This paper presents a type curve solution for a well producing from a solid bar source in an infinite-acting reservoir with impermeable upper and lower boundaries. Computation of dimensionless pressure reveals that the pressure-transient behavior of any hydraulic fracture system is governed by two critical parameters (i) aspect ratio, m, and (ii) dimensionless length, LD. Analysis of a typical log-log plot of pwD vs. tDxf indicated the existence of four distinct flow periods (i) fracture fill-up period causing a typical storage dominated flow, (ii) vertical linear flow period, (iii) transition period, and (iv) radial flow period. As aspect ratio tends to zero, the fracture fill-up periods disappear resulting in typical fully/partially penetrating vertical fracture pressure response.
This analytical solution reduces to the existing fully/partially penetrating vertical fracture solution developed by Raghavan et al1 as aspect ratio tends to zero, and a horizontal fracture solution is obtained as aspect ratio tends to unity. This new horizontal fracture solution yields superior early time (tDxf &lt; 10-3) solution compared with the existing horizontal fracture solution developed by Gringarten and Ramey2, and shows excellent agreement for tDxf &gt; 10-3.
Deeper Treating Fines Control Acid Delivers Exceptional Performance in Closed-in High Gas-Oil Ratio well
Authors: De Wit A. , Ayeni O. , Oghene N. , Ayowe C. 
Published: February 2008

Abstract
Matrix acid stimulation as a production enhancement solution has had extensive application in the oil industry. However, not a high percentage of jobs come with outstanding success. In the application being discussed, the well had been stimulated twice with mixed result. While the first job was successful, the second job was not as successful. The well production had declined to as low as 148 bopd and had to be closed in for poor productivity. An analysis of production data and build up survey data confirmed well is an acid stimulation candidate. The well was then acidised with fit-for-purpose treatment recipe. Careful execution according to design yielded 7-fold production increase in the damaged, high gas-oil ratio well. The gain from the acidizing has been sustained in comparison with immediate past acidizing intervention with significant post-job oil decline. The success of the job saved about $4-5 million, being the estimated cost for workover of the well or a new well to drain the remaining reserves. The paper is based on the result as seen in this particular well but is expected that the learning can be further employed in other wells with similar diagnostics.
Physical and Economic Performance Measures in Petroleum Lease Sales & Development: A Case Study of the U.S. Gulf of Mexico Region, 1983-1999
Authors: Iledare Omowumi , Kaiser Mark 
Published: February 2008

Abstract
This paper characterizes and analyzes petroleum lease sales and development in the U.S. Gulf of Mexico OCS using estimated physical and economic measures of performance in offshore petroleum lease development. The physical performance measures we estimated include lease prospectivity index, lease expeditious index and lease development productivity. In addition, we estimated two economic performance measures, which are profitability index and internal rate of return.
Empirical analysis of lease specific data suggests the Gulf OCS is just as attractive to the big four oil and gas integrated firms as it was two decades ago. However, there is evidence of influx of new active players in petroleum lease development in the region than two decades ago. There is also strong evidence from lease prospectivity results, which suggests that the risk of lease development failure rises with firm size and water depth leases.
Regarding lease development productivity, we find that a declining pattern in productivity with firm size from big to small and a declining productivity trend over time are unmistakable. Further, there is evidence of rising lease development productivity with water depth. For all categories of leases, the productivity rate in the early 1980s was significantly higher than productivity rate in the early 1990s, notwithstanding the fact that more leases were issued and drilled in the 1980s than in the early 1990s.
In general, our estimated measures of aggregate economic performance, the profitability index and internal rates of return are relatively low in comparison to returns in the manufacturing sector during the period. The reported low profitability measures, notwithstanding, we find that aggregate annual average rate of return on all leases issued from 1983-1994 increases with water depth and across time. The same pattern, however, is not evident in the late 1990s, probably because of data limitations. Also, the aggregate average rate of return increases with firm size leases in the 1980s, but no definitive trend is apparent across firm size in the 1990s.