bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiology of Nonsterile Pharmaceutical Manufacturing
Authors: Velagaleti Ranga 
Published: March 2010

Abstract
The U.S. Pharmacopeia (USP) and Food and Drug Administration (FDA) have laid down guidelines for microbiological quality attributes for nonsterile pharmaceuticals. Other international organizations, such as the International Conference on Harmonization (ICH), authorities in Australia, and the World Health Organization (WHO) have also published guidelines on good manucaturing practice (GMP) of nonsterile pharmaceuticals. This article focuses on the U.S. and global guidelines relevant to microbiology of nonsterile manufacturing.
Synthesis of Poly(4‐vinylpyridine) Thin Films by Initiated Chemical Vapor Deposition (iCVD) for Selective Nanotrench‐Based Sensing of Nitroaromatics
Authors: Tenhaeff Wyatt E. , McIntosh Lucas D. , Gleason Karen K. 
Published: March 2010

AbstractA new nanoscale sensing concept for the detection of nitroaromatic explosives is described. The design consists of nitroaromatic‐selective polymeric layers deposited inside microfabricated trenches. As the layers are exposed to nitroaromatic vapors, they swell and contact each other to close an electrical circuit. The nitroaromatic selective polymer, poly(4‐vinylpyridine) (P4VP), is deposited in the trenches using initiated chemical vapor deposition (iCVD). P4VP is characterized for the first time as a selective layer for the absorption of nitroaromatic vapors. The Flory–Huggins equation is used to model the swelling response to nitroaromatic vapors. The Flory–Huggins interaction parameter for the P4VP–nitrobenzene system at 40 °C is 0.71 and 0.25 for P4VP–4‐nitrotoluene at 60 °C. Sensing of nitrobenzene vapors is demonstrated in a prototype device, while techniques to improve the performance of the design in terms of response time and sensitivities are described. Modeling shows that concentration and mass limits of detection of 0.95 ppb and 3 fg, respectively, can be achieved.
Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues
Authors: Shamji Mohammed F. , Setton Lori A. , Jarvis Wingrove , So Stephen , Chen Jun , Jing Liufang , Bullock Robert , Isaacs Robert E. , Brown Christopher , Richardson William J. 
Published: March 2010

AbstractObjectivePrior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin‐17 (IL‐17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue.MethodsSurgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions.ResultsImmunoreactivity for IL‐4, IL‐6, IL‐12, and interferon‐γ (IFNγ) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL‐17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes.ConclusionGreater IFNγ positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL‐17 is a novel finding that contrasts markedly with low levels of IL‐17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration.
Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis
Authors: Rosenkranz Margalit E. , Wilson David C. , Marinov Anthony D. , Decewicz Alisha , Grof‐Tisza Patrick , Kirchner David , Giles Brendan , Reynolds Paul R. , Liebman Michael N. , Kolli V. S. Kumar , Thompson Susan D. , Hirsch Raphael 
Published: March 2010

AbstractObjectiveJuvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases, and no clinically useful prognostic markers to predict disease outcome in children with JIA are currently available. Synovial fluid likely reflects the proteins present in the inflamed synovium. The purpose of this study was to delineate the synovial fluid proteome and determine whether protein expression differs in the different subtypes of JIA.MethodsSynovial fluid samples obtained from children with oligoarticular JIA, polyarticular JIA, or systemic JIA were compared. Two‐dimensional gel electrophoresis for protein separation and matrix‐assisted laser desorption ionization−time‐of‐flight mass spectrometry and quadripole time‐of‐flight mass spectrometry for protein identification were used for this study. Synovial fluid cells were analyzed by polymerase chain reaction (PCR) for the presence of haptoglobin messenger RNA (mRNA).ResultsThe synovial fluid proteome of the samples was delineated. The majority of proteins showed overexpression in JIA synovial fluid as compared with noninflammatory control samples. There were 24 statistically significantly differentially expressed spots (>2‐fold change; P < 0.05) between the subtypes of JIA. PCR analysis revealed haptoglobin mRNA, suggesting that haptoglobin is locally produced in an inflamed joint in JIA.ConclusionDespite the similar histologic appearance of inflamed joints in patients with different subtypes of JIA, there are differences in protein expression according to the subtype of JIA. Haptoglobin is differentially expressed between the subtypes of JIA and is locally produced in an inflamed joint in JIA. Haptoglobin and other differentially expressed proteins may be potential biomarkers in JIA.
Large‐scale extraction and characterization of CD271+ multipotential stromal cells from trabecular bone in health and osteoarthritis: Implications for bone regeneration strategies based on uncultured or minimally cultured multipotential stromal cells
Authors: Jones E. , English A. , Churchman S. M. , Kouroupis D. , Boxall S. A. , Kinsey S. , Giannoudis P. G. , Emery P. , McGonagle D. 
Published: March 2010

AbstractObjectiveTo test the hypothesis that CD45lowCD271+ bone marrow multipotential stromal cells (MSCs) are abundant in the trabecular bone niche and to explore their functional “fitness” in health and osteoarthritis (OA).MethodsFollowing enzymatic extraction, MSC release was evaluated using colony‐forming unit–fibroblast (CFU‐F) and colony‐forming unit–osteoblast assays, flow cytometry, and confocal microscopy. CD45lowCD271+ cells isolated by fluorescence‐activated cell sorting were enumerated and expanded under standard and clonal conditions. Their proliferative and osteogenic potencies were assessed in relation to donor age and compared with those of aspirated CD45lowCD271+ cells. In vitro and in vivo MSC “aging” was measured using quantitative polymerase chain reaction–based telomere length analysis, and standard differentiation assays were utilized to demonstrate multipotentiality.ResultsCellular isolates from trabecular bone cavities contained ∼65‐fold more CD45lowCD271+ cells compared with aspirates (P < 0.0001) (median 1.89% [n = 39] and 0.029% [n = 46], respectively), concordant with increased CFU‐F release. Aspirated and enzymatically released CD45lowCD271+ cells had identical MSC phenotypes (∼100% CD73+CD105+CD13+, ∼50–60% CD146+CD106+CD166+) and contained large proportions of highly clonogenic multipotential cells. In vitro osteogenic potency of freshly isolated CD45lowCD271+ cells was comparable with, and often above, that of early‐passage MSCs (8–14%). Their frequency and in vivo telomere status in OA bone were similar to those in bone from age‐matched controls.ConclusionOur findings show that CD45lowCD271+ MSCs are abundant in the trabecular bone cavity and indistinguishable from aspirated CD45lowCD271+ MSCs. In OA they display aging‐related loss of proliferation but no gross osteogenic abnormality. These findings offer new opportunities for direct study of MSCs in musculoskeletal diseases without the requirement for culture expansion. They are also relevant for direct therapeutic exploitation of prospectively isolated, minimally cultured MSCs in trauma and OA.
Constructing business profiles based on keyword patterns on Web sites
Authors: Vaughan Liwen , Tang Juan , Du Jian 
Published: March 2010

AbstractThe study examined the possibility of constructing business profiles (specifically, product profiles) based on keyword patterns on various types of Web sites, including a company's own Web site, blog sites, and Web sites that have particular keywords and also hyperlinks pointing to company Web sites. To test the proposed methods, we selected China's four major oil companies and two other companies that have related products. We collected three rounds of data over a 7‐month period from these three Web sources and analyzed the numbers of retrieved pages to construct business profiles. The business profiles constructed were checked against business information collected from other sources such as company annual reports and company newsletters to determine the correctness of the profiles and thus the usefulness of the proposed methods. We found that we can construct fairly accurate profiles by examining the frequency distribution of product keywords on company Web sites. Analyzing the frequency distribution of blogs on various topics was very useful in following major business events and developments during particular time periods. We also conducted qualitative content analysis for a sample of 454 Web pages retrieved from the three sources. Findings from the content analysis confirmed the conclusions from the quantitative analysis.
Low‐frequency climate variability in the Atlantic basin during the 20th century
Authors: Tourre Y. M. , Paz S. , Kushnir Y. , White W. B. 
Published: March 2010

AbstractFrom joint sea surface temperature/sea level pressure (SST/SLP) EOF analyses, low‐frequency variability modes are compared. The multi‐decadal oscillation (MDO) changed phases twice during the 20th century, with its north Atlantic SST patterns resembling the Atlantic multi‐decadal oscillation (AMO). The quasi‐decadal oscillation (QDO) SST patterns displayed a double tripole configuration over the entire Atlantic basin, leading to tropical inter‐hemispheric out‐of‐phase relationship. From the mid‐1960s onward, while SST anomalies were negative to the north (negative phases of MDO/AMO), the Sahelian drought persisted with a weaker hurricane power dissipation index (PDI). During that period, the QDO modulated the intensity of the Sahelian drought. Copyright © 2010 Royal Meteorological Society
Severity of urban transit bus crashes in Bangladesh
Authors: Barua Upal , Tay Richard 
Published: March 2010

AbstractUnlike in developed countries where buses are a relatively safe mode of transport, there is a significant safety concern in many developing countries like Bangladesh regarding transit buses. Nevertheless, few studies have examined the factors contributing to the number or severity of bus crashes. Using the ordered probit model on bus crash data from 1998 to 2005 in Dhaka, Bangladesh, our study shows that there is a general increase in the severity of transit bus crashes over this period. Also, crash severity tends to increase when the collision occurs on weekends, off‐peak periods, and two‐way streets or involves only one vehicle, a pedestrian, and other vulnerable road users. On the other hand, the severity of a crash tends to be lower at locations with some form of police control or road medians, as well as for crashes involving hit object, parked vehicles, or sideswipes. Copyright © 2010 John Wiley & Sons, Ltd.
Anatomy of Long‐Lasting Love Affairs with Lithium Carbenoids: Past and Present Status and Future Prospects
Authors: Capriati Vito , Florio Saverio 
Published: March 2010

AbstractAfter a long adolescence, the chemistry of lithium carbenoids has currently been entering its maturity bringing a dowry of a more in‐depth and less empirical knowledge of the structure and configurational stability of such double‐faced intermediates; this, thanks in particular to the synergistic and harmonic cooperation between calculations and the most modern NMR techniques now at our disposal. Such knowledge has stimulated the development of fruitful stereoselective applications in the field of organic synthesis, providing in addition a rationale to observed selectivities. Such aspects together with the role played by aggregation and solvation on the structure–reactivity relationship are highlighted throughout this Minireview with selected examples extracted from recent literature.
General Method for the 11C‐Labeling of 2‐Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs Expression
Authors: Takashima‐Hirano Misato , Shukuri Miho , Takashima Tadayuki , Goto Miki , Wada Yasuhiro , Watanabe Yasuyoshi , Onoe Hirotaka , Doi Hisashi , Suzuki Masaaki 
Published: March 2010

AbstractCyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate 11C radionuclide into various 2‐arylpropionic acids that have a common methylated structure, particularly among nonsteroidal anti‐inflammatory drugs (NSAIDs). Thus, we developed a novel 11C‐radiolabeling methodology based on rapid C‐[11C]methylation by the reaction of [11C]CH3I with enolate intermediates generated from the corresponding esters under basic conditions. One‐pot hydrolysis of the above [11C]methylation products also allows the synthesis of desired 11C‐incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [11C]Ibuprofen, [11C]Naproxen, [11C]Flurbiprofen, [11C]Fenoprofen, [11C]Ketoprofen, and [11C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)‐induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [11C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general 11C‐labeling of 2‐arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression.
Total Synthesis and Configurational Assignment of Chondramide A
Authors: Schmauder Anke , Sibley L. David , Maier Martin E. 
Published: March 2010

AbstractThe first total synthesis of the cyclodepsipeptide chondramide A (2 b) is described. This depsipeptide is composed of four subunits, namelyL‐alanine,N‐Me‐D‐tryptophan, 3‐amino‐2‐methoxy‐propionic acid (β‐tyrosine derivative), and a 7‐hydroxy‐alkenoic acid. While the configuration of the stereogenic centers in the 7‐hydroxy‐alkenoic acid were known, the configuration of the tyrosine derivative required clarification and turned out to be (2S,3R) or (2L,3L), respectively. The synthesis of the 3‐amino‐2‐methoxy‐3‐arylpropanoic ester20 brelied on an asymmetric dihydroxylation yielding diolent‐15 afollowed by a regioselective Mitsunobu substitution leading to 3‐azido‐2‐hydroxypropanoate18 b. We could also show that the ester bond in the seco compound26 bcan be fashioned by a Mitsunobu esterification by using hydroxy ester (7S)‐7and the tripeptide acid25 b. This synthesis should allow for the preparation of various analogues.
3,3′‐diaryl‐BINOL phosphoric acids as enantioselective extractants of benzylic primary amines
Authors: Verkuijl Bastiaan J.V. , de Vries Johannes G. , Feringa Ben L. 
Published: March 2010

AbstractWe report that 3,3′‐diaryl‐BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid–liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3′‐positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV–Vis, and CD spectroscopy, which provided insight into the structure of the host–guest complex involved in extraction. Chirality 2011. © 2010 Wiley‐Liss, Inc.
Contaminated normal modeling with application to microarray data analysis
Authors: Dai Hongying , Charnigo Richard 
Published: March 2010

AbstractA contaminated beta model$(1-\gamma) B(1,1) + \gamma B(\alpha,\beta)$is often used to describe the distribution of$P$‐values arising from a microarray experiment. The authors propose and examine a different approach: namely, using a contaminated normal model$(1-\gamma) N(0,\sigma^2) + \gamma N(\mu,\sigma^2)$to describe the distribution of$Z$statistics or suitably transformed$T$statistics. The authors then address whether a researcher who has$Z$statistics should analyze them using the contaminated normal model or whether the$Z$statistics should be converted to$P$‐values to be analyzed using the contaminated beta model. The authors also provide a decision‐theoretic perspective on the analysis of$Z$statistics.The Canadian Journal of Statistics38: 315–332; 2010 © 2010 Statistical Society of Canada
Intensity‐modulated radiotherapy outcomes for oropharyngeal squamous cell carcinoma patients stratified by p16 status
Authors: Shoushtari Asal , Meeneghan Mathew , Sheng Ke , Moskaluk Christopher A. , Thomas Christopher Y. , Reibel James F. , Levine Paul A. , Jameson Mark J. , Keene Kimberly , Read Paul W. 
Published: March 2010

AbstractBACKGROUND:Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with intensity‐modulated radiotherapy (IMRT) were stratified by p16 status, neck dissection, and chemotherapy to correlate these factors with outcomes.METHODS:A total of 112 patients with OPSCC treated with IMRT from 2002 to 2008 were retrospectively analyzed. All patients received RT to 66‐70 Gray. Forty‐five of the tumors were p16 positive (p16+), 27 were p16 negative (p16−), and 41 had unknown p16 status. Sixty‐two patients had postradiation neck dissections. Nine patients with p16− tumors and 28 patients with p16+ tumors received chemotherapy. The distribution of T, N, and stage grouping among the p16+ and p16− patients was not significantly different, and 87.5% patients had stage III/IV disease.RESULTS:The median follow‐up was 26.3 months. For patients with p16+ tumors, p16− tumors, and the overall cohort, the actuarial 3‐year locoregional progression‐free survival rate was 97.8%,73.5%, and 90.5% respectively (P = .006) and the disease‐free survival rate was 88.2%, 61.4%, and 81.7%, respectively (P = .004). Patients with p16+ tumors had an 89.5% and 87.5% pathologic complete response (CR) on neck dissection with and without chemotherapy, respectively. In contrast, patients with p16− tumors had a 66.7% and 25.0% pathologic CR on neck dissection with and without chemotherapy, respectively.CONCLUSIONS:In this series, p16 status was found to be a significant predictive biomarker and patients with p16+ tumors had much better outcomes than patients with p16− tumors. Further investigation is warranted to determine whether less intense therapy is appropriate for selected patients with p16+ OPSCC, whereas more aggressive strategies are needed to improve outcomes in patients with p16− disease. Cancer 2010. © 2010 American Cancer Society.
A phase 2 study of a fixed combination of uracil and ftorafur and leucovorin given orally in a twice‐daily regimen to treat patients with recurrent metastatic breast cancer
Authors: Hortobagyi Gabriel N. , Young Robyn R. , Karwal Mark , Ibrahim Nuhad K. , Hermann Robert , Murray James L. , Watkins Stanley P. , Gore Ira 
Published: March 2010

AbstractBACKGROUND:UFT, a combination of uracil and ftorafur, was developed to combine the cytotoxic effects of 5‐fluorouracil (5‐FU) with convenient oral dosing. Leucovorin is combined with UFT to further potentiate the effect of 5‐FU on tumor cells. Orally administered UFT and leucovorin provide higher peak plasma concentrations of 5‐FU and prolonged therapeutic 5‐FU concentrations compared with continuous infusion of 5‐FU.METHODS:Ninety‐four patients with metastatic breast cancer who had been previously treated with anthracyclines and/or taxanes were treated with UFT and leucovorin, given orally, for the first 28 days of a 35‐day cycle. The total daily dose of UFT was 300 mg/m2, which was given in 2 divided doses every 12 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (OR = complete response [CR] + partial response [PR]) and overall survival (OS).RESULTS:Of the 94 patients enrolled, 68 were evaluable for efficacy. Although no CRs were observed, 9 patients achieved PRs, for an OR of 13.2% in the evaluable population. The median TTP for the evaluable population was 10.3 weeks, and the proportion of patients free of disease progression at 6 months was 17%. The median OS was 61.6 weeks for all patients enrolled. The most common drug‐related ≥ grade 3 adverse events (graded using the National Cancer Institute Common Toxicity Criteria version 2) were diarrhea, asthenia, nausea, and dehydration.CONCLUSIONS:The combination of UFT and leucovorin administered orally in a twice‐daily regimen was found to have modest activity. Grade 3 toxicities were manageable with appropriate dose adjustments in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes. Cancer 2010. © 2010 American Cancer Society.