bluuebunny/crossref_metadata_2025 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

Bruton 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

Rituximab, 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

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

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

Introduction

Imported 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.

Methods

We 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.

Results

Thirty-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.

Conclusion

This 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.
Steroid Hormones Control Circadian Elovl3 Expression in Mouse Liver
Authors: Brolinson Annelie , Fourcade Stéphane , Jakobsson Andreas , Pujol Aurora , Jacobsson Anders
Published: February 2008

The Elovl3 gene belongs to the Elovl gene family, which encodes for enzymes involved in the elongation of very long chain fatty acids. The recognized role for the enzyme is to control the elongation of saturated and monounsaturated fatty acids up to 24 carbons in length. Elovl3 was originally identified as a highly expressed gene in brown adipose tissue on cold exposure. Here we show that hepatic Elovl3 mRNA expression follows a distinct diurnal rhythm exclusively in mature male mice, with a sharp increase early in the morning Zeitgeber time (ZT) 20, peaks around ZT2, and is back to basal level at the end of the light period at ZT10. In female mice and sexually immature male mice, the Elovl3 expression was constantly low. Fasting and refeeding mice with chow or high-fat diet did not alter the Elovl3 mRNA levels. However, animals that were exclusively fed during the day for 9 d displayed an inverted expression profile. In addition, we show that Elovl3 expression is transcriptionally controlled and significantly induced by the exposure of the synthetic glucocorticoid dexamethasone. Taken together, these data suggest that Elovl3 expression in mouse liver is under strict diurnal control by circulating steroid hormones such as glucocorticoids and androgens. Finally, Elovl3 expression was found to be elevated in peroxisomal transporter ATP-binding cassette, subfamily D(ALD), member 2 ablated mice and suppressed in ATP-binding cassette subfamily D(ALD) member 2 overexpressing mice, implying a tight cross talk between very long chain fatty acid synthesis and peroxisomal fatty acid oxidation.
Glycemic Control Modulates Arginine and Asymmetrical-Dimethylarginine Levels during Critical Illness by Preserving Dimethylarginine-Dimethylaminohydrolase Activity
Authors: Ellger Björn , Richir Milan C. , van Leeuwen Paul A. M. , Debaveye Yves , Langouche Lies , Vanhorebeek Ilse , Teerlink Tom , Van den Berghe Greet
Published: February 2008

In the context of the hypercatabolic response to stress, critically ill patients reveal hyperglycemia and elevated levels of asymmetrical-dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases. Both hyperglycemia and elevated ADMA levels predict increased morbidity and mortality. Tight glycemic control by intensive insulin therapy lowers circulating ADMA levels, and improves morbidity and mortality. Methylarginines are released from proteins during catabolism. ADMA is predominantly cleared by the enzyme dimethylarginine-dimethylaminohydrolase (DDAH) in different tissues, whereas its symmetrical isoform (SDMA) is cleared via the kidneys. Therefore, glycemic control or glycemia-independent actions of insulin on protein breakdown and/or on DDAH activity resulting in augmented ADMA levels may explain part of the clinical benefit of intensive insulin therapy. Therefore, we investigated in our animal model of prolonged critical illness the relative impact of maintaining normoglycemia and of glycemia-independent action of insulin over 7 d in a four-arm design on plasma and tissue levels of ADMA and SDMA, on proteolysis as revealed by surrogate parameters as changes of body weight, plasma urea to creatinine ratio, and plasma levels of SDMA, and on tissue DDAH activity. We found that ADMA levels remained normal in the two normoglycemic groups and increased in hyperglycemic groups. SDMA levels in the investigated tissues remained largely unaffected. The urea to creatinine ratio indicated reduced proteolysis in all but normoglycemic/normal insulin animals. DDAH activity deteriorated in hyperglycemic compared with normoglycemic groups. Insulin did not affect this finding independent of glycemic control action. Conclusively, maintenance of normoglycemia and not glycemia-independent actions of insulin maintained physiological ADMA plasma and tissue levels by preserving physiological DDAH activity.
Sex-Specific Effects of Gonadectomy and Hormone Treatment on Acquisition of a 12-Arm Radial Maze Task by Sprague Dawley Rats
Authors: Gibbs Robert B. , Johnson David A.
Published: February 2008

The effects of gonadectomy and hormone treatment on spatial learning were evaluated in adult male and female rats using a modified version of a 12-arm radial maze task. In this version, procedures were used to minimize the effectiveness of strategies less reliant on working and reference memory. Results demonstrate significant sex differences favoring male performance on the working memory component of the task. In contrast, females performed slightly better than males on the reference memory component of the task. In females, ovariectomy produced a decrease in overall accuracy (i.e. an increase in the number of arm entries necessary to obtain all food pellets) as well as declines in working and reference memory performance. Both accuracy and working memory performance, but not reference memory performance, were restored by estradiol treatment. In males, castration impaired working memory performance but did not significantly affect overall accuracy or reference memory performance. Surprisingly, all groups of males performed poorly on the reference memory component of the task, and testosterone treatment appeared to worsen, rather than improve, both accuracy and reference memory performance in males. This may reflect a male preference for certain strategies that were rendered ineffective on this task. Significant sex differences, as well as treatment effects, on arm preference patterns were also detected; however, these differences were not sufficient to account for the effects of sex and treatment on acquisition. Collectively, the data demonstrate robust effects of gonadectomy and hormone treatment on acquisition of this modified radial arm maze task in females, with lesser effects in males.
Gonadotropin Stimulation of Ovarian Fractalkine Expression and Fractalkine Augmentation of Progesterone Biosynthesis by Luteinizing Granulosa Cells
Authors: Zhao Ping , De Ananya , Hu Zeng , Li Jing , Mulders Sabine M. , Sollewijn Gelpke Maarten D. , Duan En-Kui , Hsueh Aaron J. W.
Published: February 2008

Recent studies indicated that ovarian functions are regulated by diverse paracrine factors induced by the preovulatory increases in circulating LH. Based on DNA microarray analyses and real-time RT-PCR, we found a major increase in the transcript levels of a chemokine fractalkine after human chorionic gonadotropin (hCG) treatment during the preovulatory period in gonadotropin-primed immature mice and rats. Although CX3CR1, the seven-transmembrane receptor for fractalkine, was also found in murine ovaries, its transcripts displayed minimal changes. Using tandem RT-PCR and immunohistochemistry, fractalkine transcripts and proteins were localized in cumulus, mural granulosa, and theca cells as well as the oocytes, whereas CX3CR1 was found in the same cells except the oocyte. Real-time RT-PCR further indicated the hCG induction of fractalkine transcripts in different ovarian compartments, with the highest increases found in granulosa cells. In cultured granulosa cells, treatment with fractalkine augmented hCG stimulation of progesterone but not estradiol and cAMP biosynthesis with concomitant increases in transcript levels for key steroidogenic enzymes (steroidogenic acute regulatory protein, CYP11A, and 3β-hydroxysteroid dehydrogenase). In cultured preovulatory follicles, treatment with fractalkine also augmented progesterone production stimulated by hCG. Furthermore, treatment with fractalkine augmented the phosphorylation of P38 MAPK in cultured granulosa cells. The present data demonstrated that increases in preovulatory LH/hCG induce the expression of fractalkine to augment the luteinization of preovulatory granulosa cells and suggest the fractalkine/CX3CR1 signaling system plays a potential paracrine/autocrine role in preovulatory follicles.
Astrocyte Leptin Receptor (ObR) and Leptin Transport in Adult-Onset Obese Mice
Authors: Pan Weihong , Hsuchou Hung , He Yi , Sakharkar Amul , Cain Courtney , Yu Chuanhui , Kastin Abba J.
Published: February 2008

The agouti viable yellow (Avy) spontaneous mutation generates an unusual mouse phenotype of agouti-colored coat and adult-onset obesity with metabolic syndrome. Persistent production of agouti signaling protein in Avy mice antagonizes melanocortin receptors in the hypothalamus. To determine how this disruption of neuroendocrine circuits affects leptin transport across the blood-brain barrier (BBB), we measured leptin influx in Avy and B6 control mice after the development of obesity, hyperleptinemia, and increased adiposity. After iv bolus injection, 125I-leptin crossed the BBB significantly faster in young (2 month old) B6 mice than in young Avy mice or in older (8 month old) mice of either strain. This difference was not observed by in situ brain perfusion studies, indicating the cause being circulating factors, such as elevated leptin levels or soluble receptors. Thus, Avy mice showed peripheral leptin resistance. ObRa, the main transporting receptor for leptin at the BBB, showed no change in mRNA expression in the cerebral microvessels between the age-matched (2 month old) Avy and B6 mice. Higher ObRb mRNA was seen in the Avy microvasculature with unknown significance. Immunofluorescent staining unexpectedly revealed that many of the ObR(+) cells were astrocytes and that the Avy mice showed significantly more ObR(+) astrocytes in the hypothalamus than the B6 mice. Although leptin permeation from the circulation was slower in the Avy mice, the increased ObR expression in astrocytes and increased ObRb mRNA in microvessels suggest the possibility of heightened central nervous system sensitivity to circulating leptin.
Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration inC. elegans
Authors: Gabel Christopher V. , Antoine Faustine , Chuang Chiou-Fen , Samuel Aravinthan D. T. , Chang Chieh
Published: February 2008

The molecular and cellular mechanisms that allow adult-stage neurons to regenerate following damage are poorly understood. Recently, axons of motoneurons and mechanosensory neurons in adult C. elegans were found to regrow after being snipped by femtosecond laser ablation. Here, we explore the molecular determinants of adult-stage axon regeneration using the AVM mechanosensory neurons. The first step in AVM axon development is a pioneer axonal projection from the cell body to the ventral nerve cord. We show that regeneration of the AVM axon to the ventral nerve cord lacks the deterministic precision of initial axon development, requiring competition and pruning of unwanted axon branches. Nevertheless, axons of injured AVM neurons regrow to the ventral nerve cord with over 60% reliability in adult animals. In addition, in contrast to initial development, axon guidance during regeneration becomes heavily dependent on cytoplasmic protein MIG-10/Lamellipodin but independent of UNC-129/TGF-β repellent and UNC-40/DCC receptor, and axon growth during regeneration becomes heavily dependent on UNC-34/Ena and CED-10/Rac actin regulators. Thus, C. elegans may be used as a genetic system to characterize novel cellular and molecular mechanisms underlying adult-stage nervous system regeneration.
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

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 <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.
North Korea in 2007: Shuffling in from the Cold
Authors: Haggard Stephan , Noland Marcus
Published: February 2008

The year 2007 witnessed a gradual rapprochement between North Korea and the world, reflecting changes both in the country's external environment and domestic political economy. Key markers were the resumption of the Six-Party Talks and the second North-South summit. Whether these developments will endure depends largely on North Korean intentions.
Russia and the CIS in 2007: Putin's Final Year?
Authors: Ziegler Charles E.
Published: February 2008

Russia in 2007 moved further away from a constitutional order governed by the rule of law as President Vladimir Putin's second term drew to a close and the country prepared for parliamentary and presidential elections. High oil and gas prices buoyed the economy, but little progress was made in addressing Russia's serious social problems. In foreign policy, confrontation with the West was balanced by excellent relations with most of Asia.
Bangladesh in 2007: Democracy Interrupted, Political and Environmental Challenges Ahead
Authors: Hagerty Devin T.
Published: February 2008

Bangladesh hovered between democracy and dictatorship in 2007. January elections were postponed, emergency rule was declared, and an army-supported caretaker government suspended political activity and launched a massive anti-corruption campaign. Former Prime Ministers Begum Khaleda Zia and Sheikh Hasina Wajed were jailed. The government pledged to hold elections by late 2008 after institutional reforms are in place.
Nepal and Bhutan in 2007: Seeking an Elusive Consensus
Authors: Whelpton John
Published: February 2008

Amid continuing unrest in Nepal's Tarai (Lowlands) region and elsewhere, eventual abolition of the monarchy looks certain. But implementation of the country's peace process remains stalled with postponement of the Constituent Assembly elections originally scheduled for June 2007 and disagreement between the Nepali Congress Party and leftist parties over the electoral system to be adopted for these polls. In Bhutan, the process of democratization appears to be deepening and the economy is growing, but the issue of Bhutanese refugees living in Nepal continues to be an irritant both domestically and in terms of intra-state relations.
Singapore in 2007: High Wage Ministers and the Management of Gays and Elderly
Authors: Huat Chua Beng
Published: February 2008

In 2007, the People's Action Party government raised top officials' salaries, already among the highest in the world. Cultural liberalization has finally encouraged the gay community to invoke a seldom used parliamentary process to petition Parliament to repeal the Victorian law that criminalizes homosexuality. The government began to deal with some issues for an impending aging population.
Japan in 2007: A Divided Government
Authors: Govella Kristi , Vogel Steven
Published: February 2008

The ruling Liberal Democratic Party (LDP) suffered a stunning defeat in the July 2007 upper house elections, creating an unprecedented situation in which the LDP-led coalition lost its majority in the upper house while retaining a two-thirds majority in the lower house. In this new environment of “divided government” Japanese style, the LDP and the opposition jockeyed for advantage in foreign and domestic policy debates while preparing for a critical confrontation in the next lower house election.
From Chicken Little to Dr. Pangloss: William Nierenberg, Global Warming, and the Social Deconstruction of Scientific Knowledge
Authors: Oreskes Naomi , Conway Erik M. , Shindell Matthew
Published: February 2008

In recent decades, historians and sociologists of science have been largely concerned with the social construction of scientific knowledge. This paper examines an important historical episode in the social deconstruction of scientific knowledge. In the early 1980s, a consensus emerged among climate scientists that increased atmospheric carbon dioxide from burning fossil fuels would lead to mean global warming of 2–3°C, probably by the mid-twenty-first century, and would have serious deleterious effects, including sea level rise of at least seventy centimeters. This consensus was challenged, however, by a committee of the U.S. National Academy of Sciences, chaired by physicist William A. (Bill) Nierenberg, whose 1983 report arguably launched the climate change "debate." Drawing on perspectives provided by two economists on his committee, Nierenberg reframed the question not as a matter of climate change per se, but as a matter of the human capacity to adapt to change when it came, a capacity, his report asserted, that was very great. Thus, while accepting the scientific conclusion that warming would occur, Nierenberg rejected the interpretation that it would be a problem. In later years, he would play a major role in political challenges to the scientific conclusions themselves. Reframing was Nierenberg's first step on the road to the deconstruction of scientific knowledge of climate change.
The responsory: Type and modulation
Authors: Dobszay László
Published: February 2008

The responsory — a genre originated in early period of Gregorian chant, but also increasing in number until the end of the Middle Ages — is expected as transmitted in a rather stable melodic shape. The paper lists and analyses, however, 27 items with more than one melody and with variants in a wide scope of modes. In addition, 15 tunes are listed that has been adapted as contrafacta (and not as a model-melody) to new texts. These latter include not only parts of saints’ offices but also items belonging to the temporale part of the office.
After Mozart: The Viennese piano scene in the 1790s
Authors: Komlós Katalin
Published: February 2008

The last decade of the eighteenth century was a transitional period in the political as well as the cultural history of Europe. Aesthetic values underwent far-reaching changes everywhere: the field of keyboard music and keyboard performance was no exception. In Vienna, the once legendary performances of W.A. Mozart already seemed out of date for some musicians before the turn of the century. ‘Pearly’ playing gave way to singing legato style, and the occasional use of damper pedals. Of course, the appearance of the young Beethoven made a profound effect on the Viennese piano scene. He competed with four pianists on the keyboard (Gelinek, Wölfl, Steibelt, Vogler) in the course of his first ten years in Vienna: through the contemporary descriptions of these events we can learn a great deal about the current styles of piano playing. The keyboard works of the pianist-composers of the time varied in their style and level of craftsmanship. Textures became denser, and more demanding to play. The general style approached the tone of the early nineteenth century, Schubert’s in particular. Of the younger generation, Hummel was the first who performed on Viennese stages before the end of the century. After 1800, the significant Viennese debut of three young artists, Kalkbrenner, Czerny and Moscheles, initiated a new kind of bravura in pianism, which prepared the era of the instrumental virtuosity of the nineteenth century.
Nicolaus Zmeskall und die Initialen „NZ“ auf einigen Abschriften von Werken J. Haydns und A. Zimmermanns
Authors: Schirlbauer Anna
Published: February 2008

Several copies of works by Joseph Haydn and Anton Zimmermann, located mainly at the Gesellschaft der Musikfreunde in Vienna, have some striking features in common: almost identical calligraphic initials “NZ,” dates ranging from 1776 to 1778 on the cover pages, and great similarity in the handwriting of text and music. This handwriting was analysed by the author and compared to the surviving contemporary manuscript copies (paper, watermarks, script) of string quartets by Nicolaus Zmeskall (1759–1833), Beethoven’s friend in Vienna. Using previously unknown samples of Zmeskall’s handwriting from the period of his high school studies in Pressburg (Bratislava, Slovakia), it was possible to identify his music-copying style, and determine conclusively that his string quartet manuscripts are autographs. This study proves that the manuscript copies of the Haydn and Zimmermann works (including Haydn’s Violin Concerto in G Major and two symphonies by Zimmermann) were written out by Zmeskall, while he was living in Pressburg. This previously unknown aspect of Zmeskall’s biography is treated at length and it is suggested that this talented cellist and composer may have been in contact with Haydn much earlier than hitherto suspected.
„Zur Reinigung und Veredlung des Geschmacks des Volkes“ Ferenc Zsasskovszky und die Blütezeit des Musiklebens in Eger im 19. Jahrhundert
Authors: Watzatka Ágnes
Published: February 2008

Ferenc Zsasskovszky (1819–1887) wurde in Zsasskó, Nordungarn (heute Žaškov, Slowakei) als Kantorensohn geboren. Er studierte von 1841 bis 1843 an der Prager Orgelschule bei Karl Franz Pitsch, der ihn in die Kunst der Bach’schen Improvisation einführte. 1846 wurde er Regens Chori am Dom zu Eger, wo er Kirchenmusikwerke von Joseph und Michael Haydn, Mozart, Beethoven, Hummel, Cherubini etc. aufführte. Neben seiner Tätigkeit als Kantor organisierte Zsasskovszky auch weltliche Konzerte. Während dieser Zeit zählte Eger zu den bedeutendsten Musikzentren Ungarns. Zsasskovszky war auch als Pädagoge tätig, er unterrichtete Musik und leitete die Schulchöre der Lehrerbildungsanstalt, des Gymnasiums sowie der Volksschule. Zsasskovszky gab seiner Arbeit mit modernen Handbüchern eine theoretische Grundlage, die er gemeinsam mit seinem Bruder, Endre Zsasskovszky (1824–1882), verfasste. Ihr bedeutendstes Werk ist das Katholische Kirchengesangbuch (
Katholikus Egyházi Énektár
, 1855), welches den ungarischen Kirchengesang entscheidend beeinflusst hat und bis in die 1960er Jahren im regulären Gottesdienst verwendet wurde. Die Brüder Zsasskovszky verfassten Gesangbücher für alle Unterrichtsstufen und Choral-Sammlungen für alle gängigen Chorbesetzungen, die im ganzen Land verbreitet wurden und zu einem allgemeinen Aufschwung des Chorgesangs beitrugen.
The portrait of Liszt as an allegory of the artist in Ary Scheffer’s Three Magi
Authors: Kovács Imre
Published: February 2008

This study examines an allegorical painting by Ary Scheffer, the
Three Magi
, which represents Liszt posing in the guise of the youngest king, depicted in a sentimental manner. It explores the intellectual background of the picture, the meaning and the reasons behind this peculiar role-play. By identifying the portrait of Liszt with one of the three kings, Scheffer promoted the Artist to a rank that was only attainable by the Biblical kings and the monarchs of this world looking for a model of identification in them through their portraits. The painter wished to provide a pictorial form to the ideal Artist as imagined by Liszt, thus creating the spiritual portrait of the musician desiring to theoretically define himself as an artist. For this reason the painter historicized the representational type of the character of the inspired artist and ingeniously associated it with the iconographic type of the
Three Magi
. The
Three Magi
thus becoming a framework-topic, emerged as a metaphor of the concept of the Artist of the age.
The Hungarian folk song in the 18th century
Authors: Domokos Mária , Paksa Katalin
Published: February 2008

In Hungary, the concept of “folk song” was clarified at the beginning of the 20th century only, accordingly, there were no “folk songs” noted down in the 18th century. Still, the number of music sources relating to folk music increased significantly in the 18th century. As a result of their scientific analysis the melodic parallels of some five hundred 18th-century tunes were found in the central folk music collection of the Institute for Musicology of the Hungarian Academy of Sciences. These melodic parallels involve 153 folk song types. In a specific era of folk culture there is always a coexistence of elements and styles of different age. The sources also contain examples of the descending pentatonic styles (that either originates or developed from oriental roots), of the lament style and of the medieval and early modern tunes. Of particular interest are the songs that first appeared in the 17th century, then undergone significant changes in form and rich collection of variants developed around them. The most remarkable result of our research is that contrary to former beliefs regarding its insignificance, the 18th century enriched the Hungarian folk music with some sixty new melody types. One of the most interesting groups of this rather mixed collection of songs is that of the songs in a major key with a narrow compass that seems to be the most characteristic music of the time. Plagal songs in a major key with perceptive functional chords behind their melodies also entered Hungarian tradition at this time. Plagal tunes, unfamiliar to Hungarian folk music, were sometimes transformed into descending tunes. The antecedents of the new Hungarian folk song style hardly feature in these sources — this style probably developed in the late 19th century. However, among the popular art songs that flourished from the 1830s onwards we found about a dozen melody types with a partial or full similarity to 18th-century melodies.
Franz Liszts Briefe an Emilie Merian-Genast aus den Beständen des Goethe- und Schiller-Archivs, Weimar Teil 2
Authors: Hamburger Klára
Published: February 2008

Aus den größtenteils unveröffentlichten Briefen Franz Liszts entfaltet sich eine sympathische Frauengestalt. Die aus einer angesehenen weimarer Theaterfamilie stammende Mezzosopranistin Emilie Genast, eine hochmusikalische Lied- und Oratoriumsängerin, um 22 Jahre jünger als er, wurde ihm zur idealen Muse, indem sie die Lisztschen Lieder und Psalmen, die Titelrolle der
Legende von der Heiligen Elisabeth
beseelt und erfolgreich vortrug. Die Musikgeschichte hat ihr auch das Entstehen neuer Lisztscher Gesänge zu verdanken. Intim gestaltete sich das persönliche Verhältnis der beiden in der vielleicht schwersten Zeit des Vielgeprobten: nachdem die Fürstin Wittgenstein im Mai 1860 nach Rom gereist war. Der Künstler, nahe fünfzig, wusste nicht, wann und wohin er zu reisen hatte, wie er seine Laufbahn fortsetzen würde, einzig, dass seines Bleibens in Weimar nicht war — bis er endlich im Herbst 1861 nach Rom kam. 1863 heiratete Emilie Dr. Merian in Basel. Von dieser Zeit an vertiefte und veredelte sich ihre Sympathie zu einer gegenseitigen, respektvollen, bis an des Meisters Lebensende dauernden Künstlerfreundschaft.
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

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

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

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

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

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 < 10-3) solution compared with the existing horizontal fracture solution developed by Gringarten and Ramey2, and shows excellent agreement for tDxf > 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

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.