bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic diversity of citrate fermentation in Klebsiella pneumoniae
Authors: Chen Ying-Tsong , Liao Tsai-Lien , Wu Keh-Ming , Lauderdale Tsai-Ling , Yan Jing-Jou , Huang I-Wen , Lu Min-Chi , Lai Yi-Chyi , Liu Yen-Ming , Shu Hung-Yu , Wang Jin-Town , Su Ih-Jen , Tsai Shih-Feng 
Published: August 2009

Abstract

Background
It has long been recognized that Klebsiella pneumoniae can grow anaerobically on citrate. Genes responsible for citrate fermentation of K. pneumoniae were known to be located in a 13-kb gene cluster on the chromosome. By whole genome comparison of the available K. pneumoniae sequences (MGH 78578, 342, and NTUH-K2044), however, we discovered that the fermentation gene cluster was present in MGH 78578 and 342, but absent in NTUH-K2044. In the present study, the previously unknown genome diversity of citrate fermentation among K. pneumoniae clinical isolates was investigated.

Results
Using a genomic microarray containing probe sequences from multiple K. pneumoniae strains, we investigated genetic diversity among K. pneumoniae clinical isolates and found that a genomic region containing the citrate fermentation genes was not universally present in all strains. We confirmed by PCR analysis that the gene cluster was detectable in about half of the strains tested. To demonstrate the metabolic function of the genomic region, anaerobic growth of K. pneumoniae in artificial urine medium (AUM) was examined for ten strains with different clinical histories and genomic backgrounds, and the citrate fermentation potential was found correlated with the genomic region. PCR detection of the genomic region yielded high positive rates among a variety of clinical isolates collected from urine, blood, wound infection, and pneumonia. Conserved genetic organizations in the vicinity of the citrate fermentation gene clusters among K. pneumoniae, Salmonella enterica, and Escherichia coli suggest that the13-kb genomic region were not independently acquired.

Conclusion
Not all, but nearly half of the K. pneumoniae clinical isolates carry the genes responsible for anaerobic growth on citrate. Genomic variation of citrate fermentation genes in K. pneumoniae may contribute to metabolic diversity and adaptation to variable nutrient conditions in different environments.
Involvement of TORC2, a CREB co-activator, in the in vivo-specific transcriptional control of HTLV-1
Authors: Jiang Shiwen , Inada Takefumi , Tanaka Masakazu , Furuta Rika A , Shingu Koh , Fujisawa Jun-ichi 
Published: August 2009

Abstract

Background
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T -cell leukemia (ATL) but the expression of HTLV-1 is strongly suppressed in the peripheral blood of infected people. However, such suppression, which may explain the long latency in the development of ATL, is readily reversible, and viral expression resumes quickly with ex vivo culture of infected T -cells. To investigate the mechanism of in vivo -specific transcriptional suppression, we established a mouse model in which mice were intraperitoneally administered syngeneic EL4 T -lymphoma cells transduced with a recombinant retrovirus expressing a GFP-Tax fusion protein, Gax, under the control of the HTLV-1 enhancer (EL4-Gax).

Results

Gax gene transcription was silenced in vivo but quickly up-regulated in ex vivo culture. Analysis of integrated Gax reporter gene demonstrated that neither CpG methylation of the promoter DNA nor histone modification was associated with the reversible suppression. ChIP-analysis of LTR under suppression revealed reduced promoter binding of TFIIB and Pol-II, but no change in the binding of CREB or CBP/p300 to the viral enhancer sequence. However, the expression of TORC2, a co-activator of CREB, decreased substantially in the EL4-Gax cells in vivo, and this returned to normal levels in ex vivo culture. The reduced expression of TORC2 was associated with translocation from the nucleus to the cytoplasm. A knock-down experiment with siRNA confirmed that TORC2 was the major functional protein of the three TORC-family proteins (TORC1, 2, 3) in EL4-Gax cells.

Conclusion
These results suggest that the TORC2 may play an important role in the in vivo -specific transcriptional control of HTLV-1. This study provides a new model for the reversible mechanism that suppresses HTLV-1 expression in vivo without the DNA methylation or hypoacetylated histones that is observed in the primary cells of most HTLV-1 -infected carriers and a substantial number of ATL cases.
Optimal nutrition during the period of mechanical ventilation decreases mortality in critically ill, long-term acute female patients: a prospective observational cohort study
Authors: Strack van Schijndel Rob JM , Weijs Peter JM , Koopmans Rixt H , Sauerwein Hans P , Beishuizen Albertus , Girbes Armand RJ 
Published: August 2009

Abstract
Introduction
Optimal nutrition for intensive care patients has been proposed to be the provision of energy as determined by indirect calorimetry, and protein provision of at least 1.2 g/kg pre-admission weight per day. The evidence supporting these nutritional goals is based on surrogate outcomes and is not yet substantiated by patient oriented, clinically meaningful endpoints. In the present study we evaluated the effects of achieving optimal nutrition in ICU patients during their period of mechanical ventilation on mortality.

Methods
This was a prospective observational cohort study in a mixed medical-surgical, 28-bed ICU in an academic hospital. 243 sequential mixed medical-surgical patients were enrolled on day 3–5 after admission if they had an expected stay of at least another 5–7 days. They underwent indirect calorimetry as part of routine care. Nutrition was guided by the result of indirect calorimetry and we aimed to provide at least 1.2 g of protein/kg/day. Cumulative balances were calculated for the period of mechanical ventilation. Outcome parameters were ICU, 28-day and hospital mortality.

Results
In women, when corrected for weight, height, Apache II score, diagnosis category, and hyperglycaemic index, patients who reached their nutritional goals compared to those who did not, showed a hazard ratio (HR) of 0.199 for ICU mortality (CI 0.048–0.831; P = 0.027), a HR of 0.079 for 28 day mortality (CI 0.013–0.467; P = 0.005) and a HR of 0.328 for hospital mortality (CI 0.113–0.952; P = 0.04). Achievement of energy goals whilst not reaching protein goals, did not affect ICU mortality; the HR for 28 day mortality was 0.120 (CI 0.027–0.528; P = 0.005) and 0.318 for hospital mortality (CI 0.107–0.945; P = 0.039). No difference in outcome related to optimal feeding was found for men.

Conclusions
Optimal nutritional therapy improves ICU, 28-day and hospital survival in female ICU patients. Female patients reaching both energy and protein goals have better outcomes than those reaching only the energy goal. In the present study men did not benefit from optimal nutrition.
“Call for Prices”: Strategic Implications of Raising Consumers' Costs
Authors: Desai Preyas S. , Krishnamoorthy Anand , Sainam Preethika 
Published: August 2009

Many consumer durable retailers often do not advertise their prices and instead ask consumers to call them for prices. It is easy to see that this practice increases the consumers' cost of learning the prices of products they are considering, yet firms commonly use such practices. Not advertising prices may reduce the firm's advertising costs, but the strategic effects of doing so are not clear. Our objective is to examine the strategic effects of this practice. In particular, how does making price discovery more difficult for consumers affect competing retailers' price, service decisions, and profits? We develop a model in which a manufacturer sells its product through a high-service retailer and a low-service retailer. Consumers can purchase the retail service at the high-end retailer and purchase the product at the competing low-end retailer. Therefore, the high-end retailer faces a free-riding problem. A retailer first chooses its optimal service levels. Then, it chooses its optimal price levels. Finally, a retailer decides whether to advertise its prices. The model results in four structures: (1) both retailers advertise prices, (2) only the low-service retailer advertises price, (3) only the high-service retailer advertises price, and (4) neither retailer advertises price. We find that when a retailer does not advertise its price and makes price discovery more difficult for consumers, the competition between the retailers is less intense. However, the retailer is forced to charge a lower price. In addition, if the competing retailer does advertise its prices, then the competing retailer enjoys higher profit margins. We identify conditions under which each of the above four structures is an equilibrium and show that a low-service retailer not advertising its price is a more likely outcome than a high-service retailer doing so. We then solve the manufacturer's problem and find that there are several instances when a retailer's advertising decisions are different from what the manufacturer would want. We describe the nature of this channel coordination problem and identify some solutions.
Which patients with acromegaly are treated with pegvisomant? An overview of methodology and baseline data in ACROSTUDY
Authors: Brue Thierry , Castinetti Frederic , Lundgren Frida , Koltowska-Häggström Maria , Petrossians Patrick , _ _ 
Published: August 2009

Context
Pegvisomant (Somavert, Pfizer Inc.) is the first and only available GH receptor antagonist. ACROSTUDY is an international surveillance study that offers inclusion in a web-based registry to all patients with acromegaly treated with pegvisomant; it aims at monitoring long-term safety and efficacy of this compound.

Patients and methods
This report summarizes the main baseline characteristics of this particular population of patients. In February 2009, over 300 centres in 10 countries had contributed 792 patients. A gradual increase in cumulative patient recruitment was observed since the launching of ACROSTUDY in 2004: from 116 patients in 2005, it steeply increased to 792 at the latest data freeze in February 2009. At the time of enrolment, 91.8% of patients were already treated with pegvisomant but baseline was considered at the time of pegvisomant start. IGF1 concentrations were measured at local laboratories.

Results
Of all patients, 80% were reported to have had surgery and 33% to have received radiation therapy. Of the 792 patients, 14% had received no prior medical treatment before pegvisomant start, 65.9% had received somatostatin analogues and 18.6% dopamine agonists. Interestingly, 66.7% had received only pegvisomant at study start, while it was taken in association with dopamine agonists in 5.7%, with somatostatin analogues in 23.4% and with both types of agents in 3.8%. Mean IGF1 at baseline was 522 ng/ml.

Conclusion
Analysis of the baseline features of these patients treated with pegvisomant and reported in the ACROSTUDY database underscores the severity of the disease in this subset of the population of patients with acromegaly previously unresponsive to several medical, surgical or radiation treatment approaches.
The German ACROSTUDY: past and present
Authors: Buchfelder M , Schlaffer S , Droste M , Mann K , Saller B , Brübach K , Stalla G K , Strasburger C J , _ _ 
Published: August 2009

Pivotal studies have demonstrated that pharmacotherapy with pegvisomant (Somavert) is a highly effective treatment for acromegaly. Since clinical experience with the drug was very limited, the Pegvisomant Observational Study was launched in Germany immediately with the drug becoming commercially available to patients early in 2004. Its purpose was to record safety and efficacy data on as many patients as possible.
As of 12th August 2008 a total of 371 patients (185 males, 186 females) had been included in the study. They were on pegvisomant therapy for an average of 118 weeks. Median and mean doses of pegvisomant were 15 and 16.4 mg/day respectively. Treatment efficacy was monitored by IGF1 levels and the patients symptoms were evaluated by completion of a questionnaire (patient-assessed acromegaly symptom questionnaire). Safety data included liver function tests, fasting glucose, HbA1c measurements, and tumor size monitoring by repeated magnetic resonance imaging.
Normalization of IGF1 ranged from 55.7% of the 273 patients assessed after 6 months to 71.3% of 202 patients assessed after 24 months of treatment. It was 70.7% after 36 months (133 patients), 64.8% at 48 months (71 patients), and 58.4% after 60 months (24 patients). In 39 patients (10.9%) treatment was discontinued due to serious adverse events or adverse events with 25 (6.7%) of these patients having a potential causal relationship with the pegvisomant treatment. Liver function tests became abnormal in 20 patients and another three patients were recorded to have hepatobiliary disorders. Tumor size increase was reported in 20 patients, but only confirmed in nine patients by careful revision of all available images. Local injection site reactions were observed in 12 patients.
In conclusion, in this large group of pegvisomant-treated patients, long-term data for up to 5 years of treatment are now available. In 71.3% of patients with previously not sufficiently treatable acromegaly, IGF1 levels were normalized by pegvisomant therapy. Elevated transaminases usually normalized after discontinuation but in half of the affected patients also despite continuation of treatment without dose alteration. Tumor progression was a rare event. It did not exceed the expected rate in patients with acromegaly not treated with pegvisomant. As from this presently largest database of acromegalic patients treated with pegvisomant, long-term results are encouraging. The German data are now merged into the global ACROSTUDY and will constitute a major portion of the international ACROSTUDY project as a continuing global web-based observational study.
Dendritic Amplification of Stereoselectivity of a Prolinamide‐Catalyzed Direct Aldol Reaction
Authors: Mitsui Kazuhiko , Parquette Jon R. 
Published: August 2009

AbstractIsomeric “compact” and “expanded” dendrimers functionalized with L‐prolinamide catalytic units at the periphery were compared as catalysts to monomer controls in the organocatalytic direct aldol condensation. A positive dendritic effect that amplifies the stereoselectivity of the direct aldol condensation was observed for dendrimers 3 and 4, compared with lower molecular weight catalysts L‐prolinani‐lide 1 and G1 dendron 2. The difference in the compactness between 3 and 4 appears to have less impact on the stereoselectivity than the preorganized multivalency of the dendritic catalysts.
Structure–Activity Relationship Studies in Single‐Site Esterase Peptide Dendrimers
Authors: Javor Sacha , Reymond Jean‐Louis 
Published: August 2009

AbstractWe recently reported on peptide dendrimers with a single catalytic site at the dendrimer core catalyzing the hydrolysis of acetoxy‐ and butyryloxy‐pyrene trisulfonate 1a/b in aqueous buffer with Michaelis–Menten kinetics. Substrate binding is mediated by a pair of protonated arginine or histidine residues in the first generation branch, and esterolysis is performed by the imidazole side‐chain of a histidine residue in the core acting as a general base or nucleophile. Herein we report on a structure–activity relationship study searching for an optimal combination between amino acid sequence and catalytic machinery. Installation of histidine residues onto the aromatic dendrimer framework “R” leads to 10‐fold higher rate acceleration up to kcat/kuncat = 1.5 * 103 at pH 5.5 with dendrimers RG3H (AcYT)8 (BWG)4 (BHS)2BHS and RMG3H (AcYT)8(BWG)4(BHSG)2BHS (one‐letter codes for L‐amino acids; Ac = acetyl, B = L‐2,3‐diaminopropionic acid branching point, C‐terminus is amide ‐CONH2). These dendrimers reach the compactness of a native folded protein.
Synthesis and Characterization of Anionic Triazine Dendrimers with a Labile Disulfide Core
Authors: Zhang Wen , Lalwani Sanjiv , Chouai Abdellatif , Simanek Eric E. 
Published: August 2009

AbstractAnionic dendrimers based on melamine with disulfide bonds at the core were prepared to investigate the solubility of these architectures, the ability of these molecules to solubilize pyrene as a model drug, and the ability of these architectures to undergo thiol‐disulfide exchange. The ability to solubilize pyrene is directly correlated with molecular weight of the dendrimer—aggregation of dendrons does not occur. Thiol‐disulfide exchange occurs rapidly using dithiothreitol as the reductant to yield dendrimers with thiol cores that can undergo oxidation in air to yield the original dendrimer.
Self‐Assembling Dendronized Dendrimers
Authors: Percec Virgil , Imam Mohammad R. , Peterca Mihai , Cho Wook‐Dong , Heiney Paul A. 
Published: August 2009

AbstractThe amine groups from the periphery of poly(propylenimine) dendrimers [DAB‐(NH2)n] (n = 4 and 8) were reacted with the carboxylic groups of five different first and second generation self‐assembling dendrons. The amidation was mediated by the peptide bond forming reagent 2‐chloro‐4,6‐dimethoxy‐1,3,5‐triazine (CDMT)/N‐methylmorpholine (NMM). All the resulting dendronized dendrimers self‐assemble into helical pyramidal columns that self‐organize into columnar hexagonal and columnar rectangular 2D lattices and in supramolecular spheres that self‐organize into 3D Pm3n and P42/mnm tetragonal lattices. The structural and retrostructural analysis of the supramolecular dendrimers by X‐ray diffraction experiments demonstrated that supramolecular dendritic spheres are assembled from various spherical fragments, including conical and half‐sphere in which the DAB dendrimer is confined to their apex. Dendritic‐crown is the most frequently encountered conformation of the dendronized dendrimers that is responsible for the assembly of helical pyramidal columns.
Solution and Thin‐Film Aggregation Studies of Octasubstituted Dendritic Phthalocyanines
Authors: Kernag Casey A. , Mcgrath Dominic V. 
Published: August 2009

AbstractThe synthesis and solution and thin‐film characterization of eight octasubstituted dendritic phthalocyanines (Pcs) and their zinc complexes are reported. The Pc chromophore was substituted in the 2,3,9,10,16,17,23,24‐positions with three generations of benzylaryl ether dendrons with either a benzyl (3a‐3c) or 3,5‐di‐t‐butylbenzyl periphery (3d‐3f). Visible spectra in solution (CH2Cl2‐EtOH mixtures, toluene, THF, dioxane, acetone, and EtOAc) indicated a varying degree of chromophore aggregation that depended on solvent, dendrimer generation, and whether the Pc was metallated. Variable‐concentration visible spectroscopic studies were analyzed using a nonlinear least‐squares fitting procedure giving Kd values. These values further quantitated the observations that the t‐butyl‐substituted den‐drimers 3d‐3f were all less prone to aggregation in solution than the unsubstituted dendrimers 3a‐3c, with a monotonic decrease in Kd across the series 3a → 3b → 3c → 3d → 3e → 3f. Second‐generation t‐butyl‐substituted dendrimer 3f showed little to no aggregation in all solvents studied. Thin‐film studies indicated that the largest members of the two dendrimer groups, third‐generation 3c and second‐generation 3f, were largely monomeric as evidenced by split Q‐bands, similar to that seen in dilute CH2Cl2 solution when deposited via spin‐coating onto glass slides. The metallated zinc Pcs 4a‐4f all exhibited significantly less tendency toward aggregation in both solution and thin‐films than their unmetallated analogues.
Polymetallic Carbosilane Dendrimers Containing N,N'‐Iminopyridine Chelating Ligands: Applications in Catalysis
Authors: Martínez‐Olid Francisco , Benito José M. , Flores Juan C. , de Jesús Ernesto 
Published: August 2009

AbstractThis overview covers the most relevant results obtained by our group in the last few years concerning the synthesis and catalytic applications of metal complexes anchored to the surface of carbosilane dendrimers functionalized with iminopyridine ligands. Nickel dibromide complexes activated with methylaluminoxane (MAO) have been studied for the polymerization of ethylene, whereas cat‐ionic palladium(ii) derivatives have been applied to the copolymerization of carbon monoxide and tert‐butylstyrene. In addition, palladium dendrimers have been tested in the Heck reaction between methyl acrylate and iodotoluene. Correlations between the catalyst activities or reaction products (product distributions, polymer molecular weights, etc.) and the dendrimer generation are discussed and tentative explanations for these correlations provided.
Using Surrogate Biomarkers to Predict Clinical Benefit in Men with Castration-Resistant Prostate Cancer: An Update and Review of the Literature
Authors: Armstrong Andrew J. , Febbo Phillip G. 
Published: August 2009

Abstract
Recurrent prostate cancer has a complex molecular etiology and a prolonged disease course. Although initially responsive to androgen ablation, many men eventually become castration resistant, develop skeletal metastases, and are palliatively treated with docetaxel-based chemotherapy, radiation therapy, bisphosphonates, and best supportive care. Given the modest success rates of the current standard of care, clinical trial enrollment is encouraged. Castration-resistant prostate cancer (CRPC) is a heterogeneous disease, both in clinical manifestations and outcomes, requiring an individualized approach to both patient care and trial design. Herein, we review surrogate markers of disease progression and treatment efficacy in advanced prostate cancer in light of recently published guidelines that have redefined eligibility, response criteria, and suitable endpoints in prostate cancer drug development. The guidelines have refined outcome measures to potentially better capture clinical benefit and the ability of novel targeted molecular and biologic agents to impact favorably on this disease. We consider prostate-specific antigen changes, circulating tumor cells, bone scan alterations, markers of bone metabolism (urinary N-telopeptide and bone-specific alkaline phosphatase), pain improvements, and progression-free survival. To illustrate the role and challenges of these potential biomarkers and endpoints in drug development, we discuss a class of novel molecularly targeted agents, the src kinase inhibitors. Given that there are currently no validated surrogate markers of overall survival for assessing early clinical benefit from systemic therapy in metastatic CRPC, incorporation of relevant biomarkers into all phases of clinical development is essential to accelerate drug development in this field.