bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of the Yersinia pestis PhoP-PhoQ Regulatory System in the Flea and Its Role in Producing a Transmissible Infection
Authors: Rebeil Roberto , Jarrett Clayton O. , Driver James D. , Ernst Robert K. , Oyston Petra C. F. , Hinnebusch B. Joseph 
Published: February 2013

ABSTRACTTransmission ofYersinia pestisis greatly enhanced after it forms a bacterial biofilm in the foregut of the flea vector that interferes with normal blood feeding. Here we report that the ability to produce a normal foregut-blocking infection depends on induction of theY. pestisPhoP-PhoQ two-component regulatory system in the flea.Y. pestis phoP-negative mutants achieved normal infection rates and bacterial loads in the flea midgut but produced a less cohesive biofilm bothin vitroand in the flea and had a greatly reduced ability to localize to and block the flea foregut. Thus, not only is the PhoP-PhoQ system induced in the flea gut environment, but also this induction is required to produce a normal transmissible infection. The altered biofilm phenotype in the flea was not due to lack of PhoPQ-dependent or PmrAB-dependent addition of aminoarabinose to theY. pestislipid A, because an aminoarabinose-deficient mutant that is highly sensitive to cationic antimicrobial peptides had a normal phenotype in the flea digestive tract. In addition to enhancing transmissibility, induction of the PhoP-PhoQ system in the arthropod vector prior to transmission may preadaptY. pestisto resist the initial encounter with the mammalian innate immune response.
Host Cell Contact Induces Expression of Virulence Factors and VieA, a Cyclic di-GMP Phosphodiesterase, in Vibrio cholerae
Authors: Dey Amit K. , Bhagat Abha , Chowdhury Rukhsana 
Published: February 2013

ABSTRACT

Vibrio cholerae
, a noninvasive bacterium, colonizes the intestinal epithelium and secretes cholera toxin (CT), a potent enterotoxin that causes the severe fluid loss characteristic of the disease cholera. In this study, we demonstrate that adherence of
V. cholerae
to the intestinal epithelial cell line INT 407 strongly induces the expression of the major virulence genes
ctxAB
and
tcpA
and the virulence regulatory gene
toxT
. No induction of
toxR
and
tcpP
, which encode transcriptional activators of
toxT
, was observed in adhered bacteria, and the adherence-dependent upregulation of
toxT
expression was independent of ToxR and TcpP. A sharp increase in the expression of the
vieA
gene, which encodes a cyclic di-GMP (c-di-GMP) phosphodiesterase, was observed in INT 407-adhered
V. cholerae
immediately after infection. Induction of
toxT
,
ctxAB
, and
tcpA
in INT 407-adhered
vieA
mutant strain O395 Δ
vieA
was consistently lower than in the parent strain, although no effect was observed in unadhered bacteria, suggesting that VieA has a role in the upregulation of
toxT
expression specifically in host cell-adhered
V. cholerae
. Furthermore, though VieA has both a DNA binding helix-turn-helix domain and an EAL domain conferring c-di-GMP phosphodiesterase activity, the c-di-GMP phosphodiesterase activity of VieA is necessary and sufficient for the upregulation of
toxT
expression.
Immunohistochemistry improves histopathologic diagnosis in primary aldosteronism
Authors: Volpe Cristina , Höög Anders , Ogishima Tadashi , Mukai Kuniaki , Lu Ming , Thorén Marja , Hamberger Bertil 
Published: February 2013

BackgroundIn primary aldosteronism (PA) the main source of aldosterone hypersecretion is an aldosterone-producing adenoma (APA) or a bilateral hyperplasia. Histopathology of the adrenal gland from patients with PA has been difficult, as there are no morphological criteria to ascertain which are the cells that produce aldosterone. We therefore applied new specific antibodies to explore which cells in the adrenal contain the enzymes for aldosterone and cortisol production, respectively.MethodsAdrenals from 24 patients with PA were studied. After routine preparation, consecutive sections were stained with antibodies for CYP11B1 (cortisol) and CYP11B2 (aldosterone) enzymes.ResultsAPA had a strong immunoreactivity for CYB11B2. In adrenals from seven patients, we found no APA, but several nodules with strong CYB11B2 immunoreactivity, indicating aldosterone-producing nodular hyperplasia.ConclusionsImmunohistochemistry of adrenal steroidogenic enzymes provides novel diagnostic information. This may become an important part of routine histopathology, and contribute to improved clinical management in PA.
Multicenter Phase I Trial of the Mitogen-Activated Protein Kinase 1/2 Inhibitor BAY 86-9766 in Patients with Advanced Cancer
Authors: Weekes Colin D. , Von Hoff Daniel D. , Adjei Alex A. , Leffingwell Diane P. , Eckhardt S. Gail , Gore Lia , Lewis Karl D. , Weiss Glen J. , Ramanathan Ramesh K. , Dy Grace K. , Ma Wen W. , Sheedy Beth , Iverson Cory , Miner Jeffrey N. , Shen Zancong , Yeh Li-Tain , Dubowy Ronald L. , Jeffers Michael , Rajagopalan Prabhu , Clendeninn Neil J. 
Published: February 2013

Abstract
Purpose: To evaluate the safety, pharmacokinetics, and pharmacodynamics of BAY 86-9766, a selective, potent, orally available, small-molecule allosteric inhibitor of mitogen-activated protein kinase 1/2 in patients with advanced solid tumors.
Experimental Design: BAY 86-9766 was administered orally daily in 28-day courses, with doses escalated to establish the maximum-tolerated dose (MTD). An expanded cohort was evaluated at the MTD. Pharmacokinetic and pharmacodynamic parameters were assessed, with extracellular signal–regulated kinase (ERK) phosphorylation evaluated in paired biopsies from a subset of the expanded MTD cohort. Tumor specimens were evaluated for mutations in select genes.
Results: Sixty-nine patients were enrolled, including 20 patients at the MTD. The MTD was 100 mg given once-daily or in two divided doses. BAY 86-9766 was well-tolerated. The most common treatment-related toxicities were acneiform rash and gastrointestinal toxicity. BAY 86-9766 was well-absorbed after oral administration (plasma half-life ∼12 hours), and displayed dose proportional pharmacokinetics throughout the tested dose range. Continuous daily dosing resulted in moderate accumulation at most dose levels. BAY 86-9766 suppressed ERK phosphorylation in biopsied tissue and tetradecanoylphorbol acetate–stimulated peripheral blood leukocytes. Of 53 evaluable patients, one patient with colorectal cancer achieved a partial response and 11 patients had stable disease for 4 or more courses. An ocular melanoma specimen harbored a GNAQ-activating mutation and exhibited reduced ERK phosphorylation in response to therapy.
Conclusion: This phase I study showed that BAY 86-9766 was well-tolerated, with good oral absorption, dose proportional pharmacokinetics, target inhibition at the MTD, and some evidence of clinical benefit across a range of tumor types. Clin Cancer Res; 19(5); 1232–43. ©2012 AACR.
Is it possible to further improve the function of pulmonary grafts by extending the duration of lung reconditioning using ex vivo lung perfusion?
Authors: Pierre L , Lindstedt S , Hlebowicz J , Ingemansson R 
Published: February 2013

Background: The method of ex vivo lung perfusion (EVLP) has been suggested as a reliable means of differentiating between “good” and “poor” pulmonary grafts in marginal donors as, when grafts identified as good by this method are transplanted, the results do not differ from those using lungs fulfilling standard criteria. The EVLP method is also thought to improve pulmonary grafts by reducing lung edema and eliminating lung atelectasis. In the present study, we investigated whether the pulmonary graft could be further improved by extending the duration of EVLP. Methods and Materials: Six Landrace pigs were used. The lungs were reconditioned and evaluated, using the EVLP method, as double lungs. After the initial evaluation, EVLP was continued for a further 90 minutes. Results: The arterial oxygen level (pO2) was 60.8 ± 4.8 kPa after the standard 60 minutes of EVLP and 67.1 ± 2.2 kPa after 150 minutes (p = 0.48). The pulmonary vascular resistance was 453 ± 78 dyne*s/cm5 after 60, 90, 120 and 150 minutes of EVLP (p = 1.0). The pulmonary artery pressure was 17.8 ± 1.0 mmHg after 60, 90, 120, and 150 minutes of EVLP (p = 1.0) and the pulmonary artery flow was 3.5 ± 0.4 l/min after 60, 90, 120, and 150 minutes of EVLP (p = 1.0). The mean weight of the pulmonary grafts after harvesting was 574 ± 20 g at the beginning of EVLP 541 ± 24 g and, after 150 min of EVLP, 668 ± 33 (p = 0.011). Conclusions: The blood gases and hemodynamic parameters in the pulmonary grafts did not improve as a result of the extra 90 minutes of EVLP. However, the weight of the pulmonary graft increased significantly with increasing duration of EVLP, indicating lung perfusion injury.
Hiring priorities for BSW/MSW programs in the United States: Informing doctoral programs about current needs
Authors: Barsky Allan , Green Diane , Ayayo Michael 
Published: February 2013

Summary This study was designed to identify the hiring needs of social work programs across the United States. The study used a national survey of social work programs, including closed questions for quantitative analysis and an open question for qualitative comments. Findings Of the 226 MSW and BSW programs participating in this study, 95% stated that they expected to hire additional faculty in the next 5 years. The vast majority reported plans to hire at the assistant professor level. Although a PhD is a preferred degree for many programs, 62% suggested they would consider a DSW as equivalent to a PhD. Respondents suggested the most important factors influencing hiring decisions would be the candidate’s interpersonal skills, refereed publications, filling a diversity need, and supporting social work ethics. The most commonly sought areas of expertise sought include generalist practice, research/evaluation, policy, community practice, and diversity. Applications This study has implications for doctoral programs and for social workers seeking post-graduate education in the United States. One of the most interesting findings was the expressed desire for candidates with practical and practice-oriented experience. Social work departments offering research-oriented PhD degrees may want to supplement their programs by providing courses and practical experiences that prepare graduates for teaching. Departments offering DSW degrees may design their programs to fill perceived gaps in qualifications among the current pool of candidates for tenure and non-tenure positions (e.g. teaching generalist social work, advanced clinical social work, and administration). Similarly, social workers wishing to pursue academic careers should consider which types of education and experience are in greatest need. Social workers seeking academic appointments should also note that the emphasis on teaching versus research varies across institutions.
Synthesis, Structure, and Electronic Properties of Benzohexasilabicyclo[2.2.2]octene
Authors: Toma Yuki , Kuribara Takayoshi , Iizuka Takuya , Nagashima Hideo , Kyushin Soichiro 
Published: February 2013

Abstract
Benzohexasilabicyclo[2.2.2]octene was synthesized by a microwave-assisted reaction of dichlorocyclohexasilanes with 1,2-dibromobenzene in the presence of magnesium. The 1,4-cyclohexasilanylene group affects the electronic properties of the benzene ring by strong σ–π conjugation. This compound shows intense phosphorescence at 77 K.
Changes in A1C Levels Are Significantly Associated With Changes in Levels of the Cardiovascular Risk Biomarker hs-CRP
Authors: Schnell Oliver , Amann-Zalan Ildiko , Jelsovsky Zhihong , Moritz Annette , Bermejo Justo L. , Parkin Christopher G. , Schweitzer Matthias A. , Fisher Lawrence , Polonsky William H. 
Published: February 2013

OBJECTIVE
The effect of therapeutic strategies on cardiovascular (CV) disease can be evaluated by monitoring changes in CV risk biomarkers. This study investigated the effect of a structured self-monitoring of blood glucose (SMBG) protocol and the resulting improvements in glycemic control on changes in high-sensitivity C-reactive protein (hs-CRP) in insulin-naïve patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS
The Structured Testing Program (STeP) study was a prospective, cluster-randomized, multicenter trial in which 483 poorly controlled, insulin-naïve patients with type 2 diabetes were randomized to active control (ACG) or structured testing (STG) that included quarterly structured SMBG. Changes in A1C, hs-CRP, and glycemic variability (STG subjects only) were measured at baseline and quarterly.

RESULTS
Reductions in geometric mean hs-CRP values were significantly greater in the STG group at months 3 (P = 0.005), 6 (P = 0.0003), and 12 (P = 0.04) than in the ACG group. STG patients at high CV risk (&gt;3 mg/L) showed significantly greater reductions in hs-CRP levels than ACG patients at high CV risk: −3.64 mg/dL (95% CI −4.21 to −3.06) versus −2.18 mg/dL (−2.93 to −1.43), respectively (P = 0.002). There was a strong correlation between reductions in hs-CRP and A1C in both groups: standardized coefficient (β) was 0.25 for the entire cohort (P &lt; 0.0001), 0.31 for STG (P &lt; 0.0001), and 0.16 for ACG (P = 0.02).

CONCLUSIONS
Reductions in hs-CRP level are associated with reductions in A1C but not reductions in lipids or glycemic variability. Comprehensive structured SMBG-based interventions that lower A1C may translate into improvements in CV risk, as evidenced by levels of the biomarker hs-CRP.
Philip King Brown and Arequipa Sanatorium: Early Occupational Therapy as Medical and Social Experiment
Authors: Harley Lilas , Schwartz Kathleen Barker 
Published: February 2013

AbstractHistorical inquiry enriches occupational therapy practice by identifying enduring values and inspiring future excellence. This study presents for the first time the pioneering life and work of Philip King Brown, a San Francisco physician who used occupation to treat the physical, mental, and social effects of tuberculosis (TB) at Arequipa Sanatorium, the institution he founded in 1911. Through textual analysis of the Arequipa Sanatorium Records, this article evaluates and defends Brown’s assertion that his institution was medically and socially experimental. The Arequipa Sanatorium promoted occupational therapy by demonstrating its viability in the treatment of TB, the era’s most critical health threat. It also put into practice the ideals of holism, humanism, and occupational justice that resonate within the profession today. Finally, Arequipa provided an example of how an occupation program can change the public perception of disability.
Development and Validation of a Stability-Indicating Liquid Chromatography Method for the Determination of Dabigatran Etexilate in Capsules
Authors: Bernardi Raquel M , Fröehlich Pedro E , Bergold Ana M 
Published: February 2013

Abstract
An RP-LC method was developed and validated for the determination of dabigatran etexilate in a capsule formulation. The LC method was carried out on a Zorbax C18 column (250 × 4.6 mm id). The mobile phase consisted of acetonitrile and a solution of triethylamine 0.1%, pH 6.0 adjusted with phosphoric acid (65 + 35, v/v) at a flow rate of 1.0 mL/min. The diode array detector was set at 225 nm. The chromatographic separation was obtained with retention time of 6.31 min, and linearity was in the range of 10–70 μg/mL (R2 = 0.9991). The specificity and stability-indicating capability of the method was proven through degradation studies and showing that there was no interference from the excipients. The accuracy was 100.23%, with an RSD of 1.34%. The LOD and LOQ were 0.04 and 10 μg/mL, respectively. Moreover, method validation demonstrated acceptable results for robustness and a system suitability test. The proposed method was applied for the analysis of the capsules to ensure their therapeutic efficacy.
Antimycobacterial Effect of Extract and Its Components from Rheum rhaponticum
Authors: Smolarz Helena Danuta , Swatko-Ossor Marta , Ginalska Grażyna , Medyńska Ewa 
Published: February 2013

Abstract
The global threat of tuberculosis demands the search for alternative antimycobacterial drugs. The present study examined roots and petioles from Rheum rhaponticum for antimycobacterial activity. Crude methanol extracts and eight phenolic compounds isolated by preparative column chromatography were tested against Mycobacterium tuberculosisH37Ra and M. bovis using the broth dilution method. The extract from roots and its components, such as rhaponticin, deoxyrhaponticin, resveratrol, barbaloin, aloe-emodin, and chrysophanol were found to have antimycobacterial activity against both microorganisms. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration of all the investigated samples ranged from 32 to 512 μg/mL. The anthracene derivatives were the most active; their MICs were 32, 64, and 64 μg/mL (M. tuberculosisH37Ra) and 128, 64, and 64 μg/mL (M. bovis), respectively. The microorganisms were resistant to stimulation with extract from petioles, as were quercetin and rutin. The results showed that anthracene and stilbene derivatives play a prominent role in the antimycobacterial properties of R. rhaponticum.
Quality Control for Federal Clean Water Act and Safe Drinking Water Act Regulatory Compliance
Authors: Askew Ed 
Published: February 2013

Abstract
QC sample results are required in order to have confidence in the results from analytical tests. Some of the AOAC water methods include specific QC procedures, frequencies, and acceptance criteria. These are considered to be the minimum controls needed to perform the method successfully. Some regulatory programs, such as those in 40 CFR Part 136.7, require additional QC or have alternative acceptance limits. Essential QC measures include method calibration, reagent standardization, assessment of each analyst's capabilities, analysis of blind check samples, determination of the method's sensitivity (method detection level or quantification limit), and daily evaluation of bias, precision, and the presence of laboratory contamination or other analytical interference. The details of these procedures, their performance frequency, and expected ranges of results are set out in this manuscript. The specific regulatory requirements of 40 CFR Part 136.7 for the Clean Water Act, the laboratory certification requirements of 40 CFR Part 141 for the Safe Drinking Water Act, and the ISO 17025 accreditation requirements under The NELAC Institute are listed.
Bioreactors: Rotating Biological Contactors
Authors: Cortez Susana , Teixeira Pilar , Oliveira Rosário , Mota Manuel 
Published: February 2013

AbstractRotating biological contactors (RBCs) have been used as an efficient fixed film method of treating wastewater due to its advantages such as low energy and land requirements or simplicity of operation. In this article, we firstly describe the operation, benefits and drawbacks, hydrodynamics and typical applications of these bioreactors, and then review the main factors affecting their performance. Some aspects about RBC design and scale‐up, the main operational problems and their resolution are presented. The comparison of the performance of RBCs with other wastewater treatment systems as well as costs considerations and prospects are also discussed.
Process Analytical Technology: Strategies for Biopharmaceuticals
Authors: S. Rathore Anurag , Kapoor Gautam 
Published: February 2013

AbstractIn recent times, there is a growing need in the biopharmaceutical industry for improved process understanding to enhance productivity and product quality. Process Analytical Technology (PAT) is a system for designing, analyzing and controlling manufacturing processes based on an understanding of the engineering and scientific principles involved and identification of variables that affect product quality. It is based on the US FDA's belief that: “quality cannot be tested into products; it should be built‐in or should be by design.” This article provides the reader with an overview of the evolution of this technology, its key benefits and the challenges faced in its implementation. It then explains how PAT can be applied to a typical biopharmaceutical manufacturing process involving upstream and downstream processing, drug product manufacturing and chemometrics.
Differences in Innovation Between Food and Manufacturing Firms: An Analysis of Persistence
Authors: Triguero Ángela , Córcoles David , Cuerva María C. 
Published: February 2013

ABSTRACTThe authors examine the differences in the behavior of the innovation between the Spanish agrifood and manufacturing firms using firm‐level data from 1990–2008 to analyze the persistence in innovation and to explore the explanatory determinants of the probability of being product and process innovator. Survival functions, transition probability matrices, and dynamic discrete choice panel data models are combined to measure persistence. The results suggest that in the food industry the persistence of process innovation is higher than in product innovation. Environmental and market determinants such as market changes or appropriability are more decisive to explain innovation in food industry. By contrast, several determinant variables for innovation activities in the manufacturing sector seem not to be linked with the innovation in food firms. That is the case of the outsourcing ratio and the positive evolution of market share of the individual firm.
Non‐invasive UPR monitoring system and its applications in CHO production cultures
Authors: Du Zhimei , Treiber David , McCoy Rebecca E. , Miller Amanda K. , Han Mei , He Feng , Domnitz Sarah , Heath Carole , Reddy Pranhitha 
Published: February 2013

AbstractUnfolded protein response (UPR) is the primary signaling network activated in response to the accumulation of unfolded and/or misfolded protein in the endoplasmic reticulum (ER). The expression of high levels of recombinant proteins in mammalian cell cultures has been linked to the increased UPR. However, the dynamics of different UPR‐mediated events and their impact on cell performance and recombinant protein secretion during production remain poorly defined. Here, we have created a non‐invasive UPR‐responsive, fluorescence‐based reporter system to detect and quantify specific UPR‐mediated transcriptional activation of different intracellular signaling pathways. We have generated stable antibody‐expressing CHO clones containing this UPR responsive system and established FACS‐based methods for real‐time, continuous monitoring of the endogenous UPR activation in live cultures. The results showed that the UPR activation is dynamically regulated during production culture. The clones differed in their UPR patterns; both the timing and the degree of UPR‐induced transcriptional activation were linked to cell performance, such as growth, and viability. In addition, the cell culture environment, such as media composition and osmolarity, significantly impacted endogenous UPR activation. Taken together, these data demonstrate a utility of this UPR monitoring system in recombinant protein production processes and the observations increase our understanding of the critical role of UPR in regulating diverse phenotypes of the cells including growth, survival and recombinant protein secretion under different culture environments and processing conditions. Biotechnol. Bioeng. 2013; 110: 2184–2194. © 2013 Wiley Periodicals, Inc.