bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of four Neurospora crassa lytic polysaccharide monooxygenases in Pichia pastoris monitored by a fluorimetric assay
Authors: Kittl Roman , Kracher Daniel , Burgstaller Daniel , Haltrich Dietmar , Ludwig Roland 
Published: October 2012

Abstract

Background
Recent studies demonstrate that enzymes from the glycosyl hydrolase family 61 (GH61) show lytic polysaccharide monooxygenase (PMO) activity. Together with cellobiose dehydrogenase (CDH) an enzymatic system capable of oxidative cellulose cleavage is formed, which increases the efficiency of cellulases and put PMOs at focus of biofuel research. Large amounts of purified PMOs, which are difficult to obtain from the native fungal producers, are needed to study their reaction kinetics, structure and industrial application. In addition, a fast and robust enzymatic assay is necessary to monitor enzyme production and purification.

Results
Four pmo genes from Neurospora crassa were expressed in P. pastoris under control of the AOX1 promoter. High yields were obtained for the glycosylated gene products PMO-01867, PMO-02916 and PMO-08760 (>300 mg L-1), whereas the yield of non-glycosylated PMO-03328 was moderate (~45 mg L-1). The production and purification of all four enzymes was specifically followed by a newly developed, fast assay based on a side reaction of PMO: the production of H2O2 in the presence of reductants. While ascorbate is a suitable reductant for homogeneous PMO preparations, fermentation samples require the specific electron donor CDH.

Conclusions

P. pastoris is a high performing expression host for N. crassa PMOs. The pmo genes under control of the native signal sequence are correctly processed and active. The novel CDH-based enzyme assay allows fast determination of PMO activity in fermentation samples and is robust against interfering matrix components.
Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy
Authors: Rachagani Satyanarayana , Torres María P , Kumar Sushil , Haridas Dhanya , Baine Michael , Macha Muzafar A , Kaur Sukhwinder , Ponnusamy Moorthy P , Dey Parama , Seshacharyulu Parthasarathy , Johansson Sonny L , Jain Maneesh , Wagner Kay-Uwe , Batra Surinder K 
Published: October 2012

Abstract

Background
Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients.

Methods
In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (KrasG12D;Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and quantitative real-time PCR.

Results
In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I) mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p < 0.0062), CXCL1 (p < 0.00014) and CXCL2 (p < 0.08) in the pancreas of KC mice, which are known to induce mucin expression. Further, we also observed progressive increase in inflammation in pancreas of KC mice from 10 to 50 weeks of age as indicated by the increase in the macrophage infiltration. Overall, this study corroborates with previous human studies that indicated the aberrant overexpression of MUC1, MUC4 and MUC5AC mucins during the progression of PC.

Conclusions
Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC.
p130Cas/Cyclooxygenase-2 axis in the control of mesenchymal plasticity of breast cancer cells
Authors: Bisaro Brigitte , Montani Maura , Konstantinidou Georgia , Marchini Cristina , Pietrella Lucia , Iezzi Manuela , Galiè Mirco , Orso Francesca , Camporeale Annalisa , Colombo Shana M , Di Stefano Paola , Tornillo Giusy , Camacho-Leal Maria P , Turco Emilia , Taverna Daniela , Cabodi Sara , Amici Augusto , Defilippi Paola 
Published: October 2012

Abstract
Introduction
Intrinsic plasticity of breast carcinoma cells allows them to undergo a transient and reversible conversion into mesenchymal cells to disseminate into distant organs, where they can re-differentiate to an epithelial-like status to form a cohesive secondary mass. The p130Cas scaffold protein is overexpressed in human ER+ and HER2+ breast cancer where it contributes to cancer progression, invasion and resistance to therapy. However, its role in regulating mesenchymal aggressive breast cancer cells remains to be determined. The aim of this study was to investigate the molecular and functional involvement of this adaptor protein in breast cancer cell plasticity.

Methods
We used silencing strategies and rescue experiments to evaluate phenotypic and biochemical changes from mesenchymal to epithelial traits in breast tumor cell lines. In the mouse A17 cell model previously related to mesenchymal cancer stem cells and basal-like breast cancer, we biochemically dissected the signaling pathways involved and performed functional in vivo tumor growth ability assays. The significance of the signaling platform was assessed in a human setting through the use of specific inhibitors in aggressive MDA-MB-231 subpopulation LM2-4175 cells. To evaluate the clinical relevance of the results, we analyzed publicly available microarray data from the Netherlands Cancer Institute and from the Koo Foundation Sun Yat-Sen Cancer Center.

Results
We show that p130Cas silencing induces loss of mesenchymal features, by downregulating Vimentin, Snail, Slug and Twist transcriptional factors, resulting in the acquirement of epithelial-like traits. Mechanistically, p130Cas controls Cyclooxygenase-2 transcriptional expression, which in turn contributes to p130Cas-dependent maintenance of mesenchymal phenotype. This cascade of events also compromises in vivo tumor growth through inhibition of cell signaling controlling cell cycle progression. c-Src and JNK kinases are sequential players in p130Cas/ Cyclooxygenase-2 axis and their pharmacological inhibition is sufficient to downregulate Cyclooxygenase-2 leading to an epithelial phenotype. Finally, in silico microarray data analysis indicates that p130Cas and Cyclooxygenase-2 concomitant overexpression predicts poor survival and high probability of breast tumor recurrence.

Conclusions
Overall, these data identify a new p130Cas/Cyclooxygenase-2 axis as a crucial element in the control of breast tumor plasticity, opening new therapeutic strategies leading to inhibition of these pathways in aggressive breast carcinoma.
Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer
Authors: Meric-Bernstam Funda , Chen Huiqin , Akcakanat Argun , Do Kim-Anh , Lluch Ana , Hennessy Bryan T , Hortobagyi Gabriel N , Mills Gordon B , Gonzalez-Angulo Ana Maria 
Published: October 2012

Abstract
Introduction
Translation initiation is activated in cancer through increase in eukaryotic initiation factor 4E (eIF4E), eIF4G, phosphorylated eIF4E-binding protein (p4E-BP1) and phosphorylated ribosomal protein S6 (pS6), and decreased programmed cell death protein 4 (pdcd4), a translational inhibitor. Further, translation elongation is deregulated though alterations in eukaryotic elongation factor 2 (eEF2) and eEF2 kinase (eEF2K). We sought to determine the association of these translational aberrations with clinical-pathologic factors and survival outcomes in hormone receptor-positive breast cancer.

Methods
Primary tumors were collected from 190 patients with Stage I to III hormone receptor-positive breast cancer. Expression of eIF4E, eIF4G, 4E-BP1, p4E-BP1 T37/46, p4E-BP1 S65, p4E-BP1 T70, S6, pS6 S235/236, pS6 S240/244, pdcd4, eEF2 and eEF2K was assessed by reverse phase protein arrays. Univariable and multivariable analyses for recurrence-free survival (RFS) and overall survival (OS) were performed.

Results
High eEF2, S6, pS6 S240/244, p4E-BP1 T70, and low pdcd4 were significantly associated with node positivity. Median follow-up for living patients was 96 months.
High p4E-BP1 T36/47, p4E-BP1 S65, p4E-BP1 T70 and 4E-BP1 were associated with worse RFS. High p4E-BP1 T70 and pS6 S235/236, and low pdcd4, were associated with worse OS. In multivariable analysis, in addition to positive nodes, p4E-BP1 S65 remained a significant predictor of RFS (HR = 1.62, 95% CI = 1.13-2.31; P = 0.008). In addition to age, pS6 S235/236 (HR = 1.73, 95% CI = 1.03-2.90, P = 0.039), eEF2K (HR = 2.19, 95% CI = 1.35-3.56, P = 0.002) and pdcd4 (HR = 0.42, 95% CI = 0.25-0.70, P = 0.001) were associated with OS.

Conclusions
Increased pS6, p4E-BP1, eEF2K and decreased pdcd4 are associated with poor prognosis in hormone receptor-positive breast cancer, suggesting their role as prognostic markers and therapeutic targets.
Mechanisms underlying ICU muscle wasting and effects of passive mechanical loading
Authors: Llano-Diez Monica , Renaud Guillaume , Andersson Magnus , Marrero Humberto Gonzales , Cacciani Nicola , Engquist Henrik , Corpeño Rebeca , Artemenko Konstantin , Bergquist Jonas , Larsson Lars 
Published: October 2012

Abstract
Introduction
Critically ill ICU patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decreased quality of life for survivors. Critical illness myopathy (CIM) is a frequently observed neuromuscular disorder in ICU patients. Sepsis, systemic corticosteroid hormone treatment and post-synaptic neuromuscular blockade have been forwarded as the dominating triggering factors. Recent experimental results from our group using a unique experimental rat ICU model show that the mechanical silencing associated with CIM is the primary triggering factor. This study aims to unravel the mechanisms underlying CIM, and to evaluate the effects of a specific intervention aiming at reducing mechanical silencing in sedated and mechanically ventilated ICU patients.

Methods
Muscle gene/protein expression, post-translational modifications (PTMs), muscle membrane excitability, muscle mass measurements, and contractile properties at the single muscle fiber level were explored in seven deeply sedated and mechanically ventilated ICU patients (not exposed to systemic corticosteroid hormone treatment, post-synaptic neuromuscular blockade or sepsis) subjected to unilateral passive mechanical loading for 10 hours per day (2.5 hours, four times) for 9 ± 1 days.

Results
These patients developed a phenotype considered pathognomonic of CIM; that is, severe muscle wasting and a preferential myosin loss (P < 0.001). In addition, myosin PTMs specific to the ICU condition were observed in parallel with an increased sarcolemmal expression and cytoplasmic translocation of neuronal nitric oxide synthase. Passive mechanical loading for 9 ± 1 days resulted in a 35% higher specific force (P < 0.001) compared with the unloaded leg, although it was not sufficient to prevent the loss of muscle mass.

Conclusion
Mechanical silencing is suggested to be a primary mechanism underlying CIM; that is, triggering the myosin loss, muscle wasting and myosin PTMs. The higher neuronal nitric oxide synthase expression found in the ICU patients and its cytoplasmic translocation are forwarded as a probable mechanism underlying these modifications. The positive effect of passive loading on muscle fiber function strongly supports the importance of early physical therapy and mobilization in deeply sedated and mechanically ventilated ICU patients.
Choice and rejection of psychiatry as a career: surveys of UK medical graduates from 1974 to 2009
Authors: Goldacre Michael J. , Fazel Seena , Smith Fay , Lambert Trevor 
Published: October 2012

BackgroundRecruitment of adequate numbers of doctors to psychiatry is difficult.AimsTo report on career choice for psychiatry, comparing intending psychiatrists with doctors who chose other clinical careers.MethodQuestionnaire studies of all newly qualified doctors from all UK medical schools in 12 qualification years between 1974 and 2009 (33 974 respondent doctors).ResultsOne, three and five years after graduation, 4–5% of doctors specified psychiatry as their first choice of future career. This was largely unchanged across the 35 years. Comparing intending psychiatrists with doctors who chose other careers, factors with a greater influence on psychiatrists' choice included their experience of the subject at medical school, self-appraisal of their own skills, and inclinations before medical school. In a substudy of doctors who initially considered but then did not pursue specialty choices, 72% of those who did not pursue psychiatry gave ‘job content’ as their reason compared with 33% of doctors who considered but did not pursue other specialties. Historically, more women than men have chosen psychiatry, but the gap has closed over the past decade.ConclusionsJunior doctors' views about psychiatry as a possible career range from high levels of enthusiasm to antipathy, and are more polarised than views about other specialties. Shortening of working hours and improvements to working practices in other hospital-based specialties in the UK may have reduced the relative attractiveness of psychiatry to women doctors. The extent to which views of newly qualified doctors about psychiatry can be modified by medical school education, and by greater exposure to psychiatry during student and early postgraduate years, needs investigation.
Determination of Binding Constants for Inclusion Complexes of Cyclodextrins with Organic Solvents, Ethylene Glycol, and Its Related Compounds by Means of 1H NMR Spectroscopy
Authors: Yoshikiyo Keisuke , Matsui Yoshihisa , Yamamoto Tatsuyuki 
Published: October 2012

Abstract
The binding constants (Ka’s) for the complexation of α- and β-cyclodextrins (α- and β-CDs) with some hydrophilic organic solvents such as methanol, dimethyl sulfoxide, acetone, etc., were successfully determined in D2O by following changes in the 1H NMR chemical shift of the C(3)–H signal of CD, using the C(1)–H signal as an internal reference. The Ka value obtained for a β-CD–methanol complex was 0.088 mol−1 dm3 at 298 K, which is, as we know, the smallest among Ka’s measured thus far for CD complexes. The same method was also applied to the determination of Ka’s for the complexation of α-CD with ethylene glycol and some related compounds. It was revealed that these molecules were certainly included within the cavity of α-CD, though the Ka values are fairly small.
A Useful and Convenient Synthetic Protocol for Iodination of Organic Substrates Using a Combination of Vanadyl Acetylacetonate, Hydrogen Peroxide, and Sodium Iodide
Authors: Khan Abu T , Ali Shahzad 
Published: October 2012

Abstract
A wide variety of organic substrates can be iodinated selectively in good yields by employing a combination of vanadyl acetylacetonate, hydrogen peroxide, and sodium iodide at ice-bath temperature. Good yield, selectivity, use of cost effective reagents, and mild and environmentally benign reaction conditions are some of the major advantages of this protocol.
Synthesis of a Novel Ruthenium Sensitizer Bearing an ortho-Dicarboxyphenyl Group as an Anchoring Unit for Dye-sensitized Solar Cells
Authors: Ozawa Hironobu , Oura Shohei , Shimizu Ryosuke , Arakawa Hironori 
Published: October 2012

Abstract
A novel ruthenium sensitizer TUS-20, which is a structural analog of black dye, bearing an ortho-dicarboxyphenylterpyridine as an anchoring unit to TiO2 surface has been synthesized. Adsorption rate of TUS-20 was much faster, and the maximum amount of dye adsorption was larger than that of black dye. The dye-sensitized solar cell with TUS-20 exhibited 7.3% conversion efficiency under AM 1.5 (100 mW cm−2) irradiation.
Fabrication of Large Porous ZSM-5 Bulk Bodies by a One-pot Hydrothermal Method
Authors: Igi Eisaku , Kameshima Yoshikazu , Nishimoto Shunsuke , Miyake Michihiro 
Published: October 2012

Abstract
The fabrication of large ZSM-5 bulk bodies by a hydrothermal method was investigated. The results reveal that porous ZSM-5 bulk bodies with sizes of the order of centimeters could be prepared by the one-pot hydrothermal method using raw materials for synthesizing ZSM-5 powder. Machinability tests and mechanical strength measurements suggest that the bulk bodies obtained are promising as practical materials.
Gelation of Poly(l-lactic acid) Induced by Complex Crystallization with Solvents
Authors: Matsuda Yasuhiro , Fukatsu Akinobu , Tasaka Shigeru 
Published: October 2012

Abstract
Gels of poly(l-lactic acid) (PLLA) in several solvents, including N,N-dimethylformamide (DMF) were formed by cooling solutions of PLLA. Polarizing optical micrographs showed the formation of spherulites of PLLA in the gels below 70 °C. The storage modulus of the gel decreased abruptly below 70 °C, which suggest that the crystalline structure of PLLA prevented the flow of DMF and induced the gelation. The X-ray diffraction (XRD) patterns of the gels were similar to those of the ε-crystals of PLLA which were induced by the formation of complex crystallization with DMF. The mechanism of the formation of the gel is discussed based on the experimental data.
Formation of Planar Bilayer Membranes on Solid Supports Using Peptide Gemini Surfactants
Authors: Umezaki Katsunari , Sakai Shunsuke , Koeda Shuhei , Yamamoto Yasushi , Kondo Masaharu , Ikeda Atsushi , Dewa Takehisa , Taga Keijiro , Tanaka Toshiki , Mizuno Toshihisa 
Published: October 2012

Abstract
Peptide-based gemini surfactants, called PG-surfactants, consisting of a tri- or tetra-Asp peptide core and acetylated dodecylamine-conjugated Cys residues at both the N- and C-terminal ends (D3C12 and D4C12), form a stable planar bilayer membrane on a solid support. From the DLS and TEM analyses, D3C12 and D4C12 have a tendency to form bilayer morphologies in a buffer solution, which reflects their tendency to form a stable planar bilayer membrane.
Avoiding Inadvertent Intravenous Injection of Oral Liquids; Medication within Intravenous Tubing may be Overlooked; Searching by Drug Name Gives Information on Wrong Drug
Authors: Cohen Michael R. , Smetzer Judy L. 
Published: October 2012

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Which Comes First CPOE or eMAR? A Retrospective Analysis of Health Information Technology Implementation
Authors: Sullins Amanda K. , Richard Ashley A. , Manasco Kalen B. , Phillips Marjorie S. , Gomez Tad A. 
Published: October 2012

Purpose The objective of this study was to determine whether the order of implementation of computerized prescriber order entry (CPOE) and electronic medication administration records (eMAR) into a health care facility would impact the medication error rate at an academic medical center. Methods A single academic medical center implemented CPOE first in one of its facilities (CPOE-first facility) and eMAR first in the other facility (eMAR-first facility). We conducted a retrospective chart review of patients admitted during designated data collection time periods (baseline, after the first intervention, and after both CPOE and eMAR). The primary outcome was defined as the change in medication error rate from baseline to the first intervention (either CPOE or eMAR). Secondary aims included evaluating final medication error rate and the severity and origin of detected errors. Results In the eMAR-first facility, the medication error rate decreased by 22.6% from baseline after only eMAR was introduced (odds ratio [OR], 1.4; P < .05). The CPOE-first facility showed a 13.3% reduction in the medication error rate after only CPOE was introduced (OR, 1.18; P = .24). Both hospitals demonstrated a significant decrease in medication error rates from baseline to after both CPOE and eMAR were implemented. Additionally, eMAR seemed to reduce errors reaching the patient to a greater extent than CPOE. Conclusion The integration of eMAR prior to CPOE resulted in a greater reduction in medication errors during the implementation of computerized health care technology. Because eMAR also reduced errors reaching the patient, we recommend initiating health information technology implementation with eMAR prior to CPOE.
AKI in a Hospitalized Patient with Cellulitis
Authors: Perazella Mark A. 
Published: October 2012

Summary
AKI occurs commonly in hospitalized patients with multiple comorbidities. In this Attending Rounds, a woman with AKI in the setting of an infection, use of antibiotics and other medications, bacteremia, and hypotension is considered. Such patients lead to a broad differential diagnosis for AKI including prerenal AKI, acute tubular injury/acute tubular necrosis, infection-related GN, and drug-induced acute interstitial nephritis. The roles of an accurate history, physical examination, laboratory data, and kidney biopsy are highlighted in establishing the correct diagnosis in such patients.
Auditor-Provided Nonaudit Services and Audit Effectiveness and Efficiency: Evidence from Pre- and Post-SOX Audit Report Lags
Authors: Knechel W. Robert , Sharma Divesh S. 
Published: October 2012

SUMMARY
The Sarbanes-Oxley Act of 2002 (SOX) effectively bars an auditor from providing nonaudit services to an audit client based on the belief that the resulting economic bonding undermines the auditor's independence and quality of the audit (U.S. House of Representatives 2002). The accounting profession has strongly debated this view and counter-argues that auditor-provided nonaudit services benefit the client. We contribute to this debate by examining the effect of auditor-provided nonaudit services on the effectiveness and efficiency of the audit. We find that higher nonaudit service fees are associated with shorter audit report lags—a potential indicator of audit efficiency—prior to the passage of SOX, but such effects dissipate after SOX. We find that discretionary accruals and financial restatements—potential indicators of audit effectiveness—do not increase when shorter audit lags occur in conjunction with high nonaudit service fees. We also find that the firms with the highest levels of nonaudit service fees prior to SOX have the largest increase in audit lags after SOX. These results suggest that there is some merit to the profession's argument that auditor-provided nonaudit services benefit clients without leading to a loss of audit effectiveness.
Data Availability: All data are publicly available from sources identified in the text.