bluuebunny/crossref_metadata_2025 huggingface dataset:
AC13, a C‐terminal fragment of apolipoprotein A‐I, is a candidate biomarker for microscopic polyangiitis
Authors: Takakuwa Yukiko , Kurokawa Manae S. , Ooka Seido , Sato Toshiyuki , Nagai Kouhei , Arito Mitsumi , Suematsu Naoya , Okamoto Kazuki , Nagafuchi Hiroko , Yamada Hidehiro , Ozaki Shoichi , Kato Tomohiro
Published: July 2011

Objective

Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease.

Methods

Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg‐Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction.

Results

A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C‐terminal amino acid residues of apolipoprotein A‐I (Apo A‐I) and was designated “AC13.” Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A‐I and high‐density lipoprotein cholesterol were down‐regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up‐regulated secretion of interleukin‐6 (IL‐6) (P < 0.05) and IL‐8 (P < 0.01).

Conclusion

AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up‐regulation of proinflammatory cytokines.
Literature‐based discovery: Beyond the ABCs
Authors: Smalheiser Neil R.
Published: July 2011

Literature‐based discovery (LBD) refers to a particular type of text mining that seeks to identify nontrivial assertions that are implicit, and not explicitly stated, and that are detected by juxtaposing (generally a large body of) documents. In this review, I will provide a brief overview of LBD, both past and present, and will propose some new directions for the next decade. The prevalent ABC model is not “wrong”; however, it is only one of several different types of models that can contribute to the development of the next generation of LBD tools. Perhaps the most urgent need is to develop a series of objective literature‐based interestingness measures, which can customize the output of LBD systems for different types of scientific investigations.
Alternative Method of Solution of the Regulator Equation: L2‐Space Approach
Authors: Rehák B.
Published: July 2011

An alternative method for the proof of solvability of the differential equation that is a part of the regulator equation which arises from the solution of the output regulation problem. The proof uses the L2‐space based theory of solutions of partial differential equations for the case of the linear output regulation problem. In the nonlinear case, a sequence of linear equations is defined so that their solutions converge to the solution of the nonlinear problem. This is proved using the Banach Contraction Theorem.

Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Characterization of bent helical conformations in polymorphic forms of a designed 18‐residue peptide containing a central gly‐pro segment
Authors: Aravinda Subrayashastry , Shamala Narayanaswamy , Karle Isabella L. , Balaram Padmanabhan
Published: July 2011

An 18‐residue sequence Boc‐Aib‐Val‐Ala‐Leu‐Aib‐Val‐Ala‐Leu‐Gly‐Pro‐Val‐Ala‐Leu‐Aib‐Val‐Ala‐Leu‐Aib‐OMe (UK18) was designed to examine the effect of introducing a Gly‐Pro segment into the middle of a potentially helical peptide. The crystal structures of two polymorphic forms yielded a view of the conformation of three independent molecules. Form 1 (space group P212121, a = 14.620Å; b = 26.506Å, c = 28.858Å, Z = 4) has one molecule in the asymmetric unit, with one cocrystallized water molecule. Form 2 (space group P212121, a = 9.696Å; b = 19.641Å, c = 114.31Å, Z = 8) has two molecules in the asymmetric unit with four cocrystallized water molecules. In Form 1, residues 1 to 18 adopt ϕ,ψ values that lie in the right‐handed helical (αR) region of the Ramachandran map. Two residues, Leu (8) (ϕ = −92.0°, ψ = −7.5°) and Leu (17) (ϕ = −94.7°, ψ = −1.7°) adopt conformations that deviate significantly from helical values. In Form 2, molecule A, residues 2 to 16 lie in the αR region of ϕ,ψ space, with Leu (8) (ϕ = −94.9°, ψ = −2.9°) deviating significantly from helical values. Aib (1) and Aib (18) adopt left‐handed (αL) helical conformation. Significant distortion is observed at Leu (17) (ϕ = −121.3°, ψ = −31.3°). Molecule B, Form 2, adopts a right‐handed helix over residues 1 to 17. In all three molecules, a distinct bend in the helix is observed, with the bend angle values varying from 40.8° to 58.9°. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 76–86, 2012.
An amyloidogenic determinant in n‐terminal pro‐brain natriuretic peptide (nt‐probnp): Implications for cardiac amyloidoses
Authors: Iconomidou Vassiliki A. , Pheida Danae , Hamodraka Eftihia S. , Antony Claude , Hoenger Andreas , Hamodrakas Stavros J.
Published: July 2011

Deposition of amyloid in the atria (isolated atrial/cardiac amyloid) is fairly common in the aging heart. It consists of amyloid fibrils, formed both by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the precursor molecule of ANP, proANP. This study examines whether amyloidogenic determinants (short peptides/amyloid forming favoring regions) exist in the sequence of NT‐proBNP, the N‐terminal part of proBNP, and if these determinants form amyloid‐like fibrils in vitro. We have predicted a possible amyloidogenic determinant in the sequence of the NT‐proBNP, and we conclusively show, after its synthesis, that it forms amyloid‐like fibrils in vitro, utilizing transmission electron microscopy, X‐ray diffraction, attenuated total reflectance Fourier‐transform infrared spectroscopy, and polarizing microscopy. Thus, for the first time, in this study, a possible biological role is attributed to a certain, specific part of this important cardiac prohormone/natriuretic peptide, which acts as an important biomarker indicative of heart failure. Its possible direct involvement in isolated cardiac amyloidosis, atrial fibrillation, and other types of cardiac amyloidoses is indicated and discussed. Since these cardiac hormones and their prohormones play key roles in cardiovascular homeostasis through natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion (pathophysiology of hypertension and cardiovascular regulation), we also try to suggest these specific, short peptides as possible future structural targets of efforts toward inhibiting formation of natriuretic peptide(s) amyloid. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 67–75, 2012.
Computer modeling of nitroxide spin labels on proteins
Authors: Hatmal Ma'mon M. , Li Yiyu , Hegde Balachandra G. , Hegde Prabhavati B. , Jao Christine C. , Langen Ralf , Haworth Ian S.
Published: July 2011

Electron paramagnetic resonance using site‐directed spin labeling can be used as an approach for determination of protein structures that are difficult to solve by other methods. One important aspect of this approach is the measurement of interlabel distances using the double electron–electron resonance (DEER) method. Interpretation of experimental data could be facilitated by a computational approach to calculation of interlabel distances. We describe an algorithm, PRONOX, for rapid computation of interlabel distances based on calculation of spin label conformer distributions at any site of a protein. The program incorporates features of the label distribution established experimentally, including weighting of favorable conformers of the label. Distances calculated by PRONOX were compared with new DEER distances for amphiphysin and annexin B12 and with published data for FCHo2 (F‐BAR), endophilin, and α‐synuclein, a total of 44 interlabel distances. The program reproduced these distances accurately (r2 = 0.94, slope = 0.98). For 9 of the 11 distances for amphiphysin, PRONOX reproduced the experimental data to within 2.5 Å. The speed and accuracy of PRONOX suggest that the algorithm can be used for fitting to DEER data for determination of protein tertiary structure. © 2011 Wiley Periodicals, Inc. Biopolymers 97: 35–44, 2012.
Negative appendicectomy and perforation rates in patients undergoing laparoscopic surgery for suspected appendicitis (Br J Surg 2011; 98: 589–595)
Authors: Berney C
Published: July 2011

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (http://www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.
Comparison of zotarolimus‐ versus everolimus‐eluting stents in the treatment of coronary bifurcation lesions
Authors: Herrador Juan A. , Fernandez Juan C. , Guzman Manuel , Aragon Victor
Published: July 2011

Objectives: To compare zotarolimus‐eluting stent (Endeavor Sprint®; ZES‐S) and the everolimus‐eluting stent (Xience V®; EES) in the treatment of coronary bifurcation lesions Background: Both these stents have demonstrated good outcomes in the treatment of coronary lesions. However, the outcomes with respect to treatment of bifurcation lesions have yet to be conclusively demonstrated. Methods: In this single centered, nonrandomized, open label study, we treated, between August 2006 and December 2008, 110 bifurcations with ZES‐S and, in a second stage of the study, 129 bifurcations with EES. The primary end point was to compare the rate of major adverse cardiac events (MACE) (death, myocardial infarction, and new target lesion revascularization) in‐hospital and at 12 months of follow‐up. Provisional T stenting was the strategy used in the majority of cases. Angiographic follow‐up was performed only in patients who presented signs or symptoms suggestive of angina or ischemia. Results: There were no significant differences in in‐hospital MACE between the groups (ZES‐S: 8.1%; EES: 6.2%; P = 0.5). At 12 months, the ZES‐S group had significantly more MACE than the EES group (23.1% vs. 4.5%; P < 0.001) and an elevated index of new revascularization of the bifurcation (17.5% vs. 3.2%; P < 0.001). There were no significant differences in mortality (four patients in ZES‐S vs. one in EES; P = 0.14). Conclusion: The treatment of coronary bifurcation lesions using everolimus‐eluting stents results in better outcomes at 12 months of follow‐up than zotarolimus‐eluting stents. © 2011 Wiley Periodicals, Inc.
Influence of Potassium on the Synthesis of Methanethiol from Carbonyl Sulfide on Sulfided Mo/Al2O3 Catalyst
Authors: Gutiérrez Oliver Y. , Kaufmann Christoph , Lercher Johannes A.
Published: July 2011

Potassium‐doped MoS2 catalysts supported on Al2O3 were synthesized, characterized by using atomic absorption spectroscopy, N2 physisorption, NO adsorption, X‐ray diffraction, temperature‐programmed sulfidation, and Raman spectroscopy, and tested in the synthesis of methanethiol from carbonyl sulfide (COS) and H2. The results revealed that two phases, pure MoS2 and potassium‐decorated MoS2 (formed at high potassium loadings), were present in the active catalysts. The main effect of potassium during sulfidation and during the catalytic reaction was to increase the mobility of surface oxygen or sulfur atoms. Thus, potassium promoted the disproportionation of COS to CO2 and CS2 and the production of CO from CO2. Additionally, potassium cations hindered the reductive decomposition of COS to CO and H2S and the hydrogenolysis of methanethiol to methane. Mars–van Krevelen‐type mechanisms were proposed to explain the disproportionation of COS on alumina and on the MoS2 phases. The catalytic site in the potassium‐decorated MoS2 phase was proposed to include a potassium cation as adsorption site.
Conception, Synthesis, and Biological Evaluation of Original Discodermolide Analogues
Authors: de Lemos Elsa , Agouridas Evangelos , Sorin Geoffroy , Guerreiro Antonio , Commerçon Alain , Pancrazi Ange , Betzer Jean‐François , Lannou Marie‐Isabelle , Ardisson Janick
Published: July 2011

Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive “U” shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)‐diene moiety, of the methyl group at the C14‐position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.
A numerical postprocessing procedure for analyzing radio frequency MRI coils
Authors: Lemdiasov Rostislav A. , Obi Aghogho A. , Ludwig Reinhold
Published: July 2011

The design and construction of radio frequency (RF) coils for application‐specific magnetic resonance imaging purposes are generally extensive, iterative engineering endeavors that involve multiple electromagnetic simulations followed by tuning and matching on the bench. Computational models of RF coil structures typically take into account the conductor topology; however, they do not address the deployment of lumped circuit elements for tuning, matching, and decoupling. As a result, the design engineer must frequently resort to exhaustive trial‐and‐error attempts to ensure that the coil, or coil array, is functional at the target resonance frequency. Because coil losses are often not easily predictable in simulations, the final result can be an inferior prototype construction. In this article, a general numerical procedure is outlined that enables the effective simulation and performance comparison of RF coils. The procedure relies on an integrated modeling approach, which combines full‐wave electromagnetic simulations with a scattering parameter network representation of all relevant tuning, matching, and decoupling elements. With this combined distributed‐lumped simulation approach, detailed comparative studies can be conducted on the basis of a figure of merit parameter that is proportional to the signal‐to‐noise ratio. Furthermore, major loss mechanisms affecting coil performance can readily be identified and quantified. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part A 38: 133–147, 2011.
An adaptive MR‐compatible lens and objective
Authors: Maclaren J. , Schneider F. , Herbst M. , Hennig J. , Bammer R. , Zaitsev M. , Wallrabe U.
Published: July 2011

This work presents an MR‐compatible adaptive liquid lens, designed to form part of an in‐bore optical imaging system. The lens is integrated into a wide‐angle objective, which is suitable for use with a camera mounted above the head coil to monitor subject head motion. Compatibility tests indicate that focusing of the lens is unaffected by the static, gradient, or radio frequency (RF) fields of the scanner. Field mapping shows that no B0 field distortions are visible with the system mounted 55 mm above a water‐filled phantom. The total increase in RF noise observed on a 1.5‐T system when using the lens and lighting setup is less than 2%, and this is mostly attributable to the lighting. This work was originally motivated by head tracking for prospective motion correction; however, the lens may have other applications whenever high‐quality optical images are required in the MR environment and motion of the object makes a fixed lens unsuitable. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 39B: 141–148, 2011
Prolyl hydroxylase‐2 (PHD2) exerts tumor‐suppressive activity in pancreatic cancer
Authors: Su Yun , Loos Martin , Giese Natalia , Metzen Eric , Büchler Markus W. , Friess Helmut , Kornberg Arno , Büchler Peter
Published: July 2011

BACKGROUND:

Pancreatic cancer is 1 of the most common and poorly treated tumors. In search of new therapeutic approaches, the oxygen sensors prolyl hydroxylases (PHD) are potential targets. PHD2 is considered the key oxygen sensor‐regulating hypoxia‐inducible factor (HIF). Currently, there is conflicting evidence regarding the exact role of PHD2 in tumorigenesis. The objective of this study was to investigate the role of PHD2 in pancreatic cancer growth and progression.

METHODS:

PHD2 expression was analyzed by quantitative real‐time polymerase chain reaction analysis and immunohistochemistry in human tissue specimens and cell lines. Knockdown of PHD2 was done by using short‐interfering RNAs (siRNAs) specific against PHD2, and PHD2 overexpression was achieved by stable combinational DNA transfection. In vivo, an orthotopic murine model was used. Angiogenic cytokines were assessed with enzyme‐linked immunosorbent assays, and invasion was studied with Matrigel assays.

RESULTS:

PHD2 expression was not altered substantially in cancer tissues and their metastases. Lymph node‐negative tissues had higher levels of PHD2 than lymph node‐positive tissues. PHD2 was hypoxia‐inducible in pancreatic cancer cell lines and regulated cell growth through cyclin D1 down‐regulation samples with PHD2 suppression and through p21 up‐regulation in samples with of PHD2 overexpression. In vivo, PHD2 caused tumor growth retardation and reduced tumor invasion by inhibiting angiogenesis. This observation was caused by the suppression of angiogenic cytokines and tumor invasion.

CONCLUSIONS:

The current results indicated that PHD2 plays an important role in pancreatic tumorigenesis. In summary, the authors concluded that PHD2 may function as a tumor suppressor gene in pancreatic cancer and, thus, may define a potential target for the treatment of pancreatic cancer. Cancer 2012;. © 2011 American Cancer Society.
Progression‐free and overall survival in patients with relapsed/refractory germ cell tumors treated with single‐agent chemotherapy: Endpoints for clinical trial design
Authors: Feldman Darren R. , Patil Sujata , Trinos Michael J. , Carousso Maryann , Ginsberg Michelle S. , Sheinfeld Joel , Bajorin Dean F. , Bosl George J. , Motzer Robert J.
Published: July 2011

BACKGROUND:

Refractory germ cell tumor (GCT) patients have a poor prognosis and limited treatment options. The identification of novel active agents may be impaired by use of response as the primary endpoint in phase 2 trials. Improved endpoints could enhance the development of new effective agents.

METHODS:

The characteristics and outcome of refractory GCT patients enrolled in 7 single‐agent phase 2 trials conducted at Memorial Sloan‐Kettering Cancer Center from 1990 to 2008 were reviewed. The study agents were suramin, all‐transretinoic acid, topotecan, pyrazoloacridine, temozolomide, ixabepilone, and sunitinib. The major endpoints evaluated were response, progression‐free survival (PFS), and overall survival (OS).

RESULTS:

Ninety patients (87 male, 3 female) were treated. The primary tumor site was testis in 65 patients, mediastinum in 17 patients, retroperitoneum in 4 patients, and other in 4 patients. Eighty‐six patients had nonseminoma, and 4 patients had pure seminoma. Best responses were 1 (1%) partial response (ixabepilone), 15 (17%) stable disease, and 74 (82%) progressive disease. Median PFS and OS were 1.0 month (95% confidence interval [CI], 0.8‐1.3) and 4.7 months (95% CI, 3.5‐6.4), respectively. Eighty‐six of the 90 patients have died. The 12‐ and 16‐week PFS rates were 9% (95% CI, 3‐15%) and 6% (95% CI, 1%‐11%), respectively.

CONCLUSIONS:

Patients with refractory GCT progressed rapidly to these single agents. PFS and OS may be useful endpoints for designing phase 2 trials testing novel agents in this population. Twelve‐week PFS (with comparison to the 9% benchmark rate reported herein) is the recommended endpoint for phase 2 trial design and median OS (using 4.7 months as the predicted median for the control arm) is suggested for phase 3 trials. Cancer 2012;. © 2011 American Cancer Society.
A novel Haar wavelet‐based vector BPSK–OFDM robust to channel spectral nulls and with reduced cyclic prefix length and PAPR
Authors: Huang X.L. , Wang G. , Hu F.
Published: July 2011

The performance of OFDM systems may be degraded when intersymbol interference (ISI) channels have spectral nulls. The communication overhead because of the insertion of the cyclic prefix is high when ISI channels have many taps. Recently, the precoded OFDM systems and vector OFDM (VOFDM) systems were proposed to combat these two problems, respectively. This paper proposes a novel vector binary phase‐shift keying (BPSK)–OFDM system based on Haar wavelet transformation. The Haar wavelet transformation performs decomposition over the vector information symbols produced by a BPSK modulator. It shows that half of the information symbols are zero and the rest are or . Then, the vector BPSK–OFDM becomes the precoded OFDM, which inserts one or more zeros between two sets of K consecutive information symbols. This precoding scheme is able to remove the spectral nulls of an ISI channel without knowing the ISI (like conventional precoded OFDM systems), and it has the same cyclic prefix length as VOFDM systems. The proposed OFDM systems show better robustness to the spectral nulls channel, compared with the conventional VOFDM systems. Because of the insertion of (M −K) zeros between two sets of K consecutive information symbols, the conventional precoded OFDM systems have the data rate expanded and signal‐to‐noise power ratio reduced by 10 log 10(M∕K) dB compared with the proposed OFDM systems. Moreover, because half of the information symbols are zeros after Haar wavelet transformation, the proposed OFDM system can further reduce the transmitting peak‐to‐average power ratio. Finally, we compare the proposed OFDM systems with the precoded OFDM and VOFDM systems. Copyright © 2011 John Wiley & Sons, Ltd.
Predicting Dyslexia at Age 11 from a Risk Index Questionnaire at Age 5
Authors: Helland Turid , Plante Elena , Hugdahl Kenneth
Published: July 2011

This study focused on predicting dyslexia in children ahead of formal literacy training. Because dyslexia is a constitutional impairment, risk factors should be seen in preschool. It was hypothesized that data gathered at age 5 using questions targeting the dyslexia endophenotype should be reliable and valid predictors of dyslexia at age 11. A questionnaire was given to caretakers of 120 5‐year‐old children, and a risk index score was calculated based on questions regarding health, laterality, motor skills, language, special needs education and heredity. An at‐risk group (n = 25) and matched controls (n = 24) were followed until age 11, when a similar questionnaire and literacy tests were administered to the children who participated in the follow‐up study (22 at risk and 20 control). Half of the at‐risk children and two of the control children at age 5 were identified as having dyslexia at age 11 (8 girls and 5 boys). It is concluded that it is possible to identify children at the age of 5 who will have dyslexia at the age of 11 through a questionnaire approach. Copyright © 2011 John Wiley & Sons, Ltd.
Eliciting Dyslexic Symptoms in Proficient Readers by Simulating Deficits in Grapheme‐to‐Phoneme Conversion and Visuo‐Magnocellular Processing
Authors: Tholen Nicole , Weidner Ralph , Grande Marion , Amunts Katrin , Heim Stefan
Published: July 2011

Among the cognitive causes of dyslexia, phonological and magnocellular deficits have attracted a substantial amount of research. Their role and their exact impact on reading ability are still a matter of debate, partly also because large samples of dyslexics are hard to recruit. Here, we report a new technique to simulate dyslexic symptoms in normal readers in two ways. Although difficulties in grapheme‐to‐phoneme conversion were elicited by manipulating the identifiability of written letters, visual‐magnocellular processing deficits were generated by presenting letters moving dynamically on the screen. Both factors were embedded into a lexical word–pseudoword decision task with proficient German readers. Although both experimental variations systematically increased lexical decision times, they did not interact. Subjects successfully performed word–pseudoword distinctions at all levels of simulation, with consistently longer reaction times for pseudowords than for words. Interestingly, detecting a pseudoword was more difficult in the grapheme‐to‐phoneme conversion simulation as indicated by a significant interaction of word type and letter shape. These behavioural effects are consistent with those observed in ‘real’ dyslexics in the literature. The paradigm is thus a potential means of generating novel hypotheses about dyslexia, which can easily be tested with normal readers before screening and recruiting real dyslexics. Copyright © 2011 John Wiley & Sons, Ltd.
Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs
Authors: Meza‐Sánchez David , Pérez‐Montesinos Gibrán , Sánchez‐García Javier , Moreno José , Bonifaz Laura C.
Published: July 2011

The nature of CD4+ T‐cell responses after skin immunization and the role of migrating DCs in the presence of adjuvants in the elicited response are interesting issues to be investigated. Here, we evaluated the priming of CD4+ T cells following ear immunization with low doses of model antigens in combination with either cholera toxin (CT) or the non‐toxic β CT subunit (CTB) as an adjuvant. Following immunization with CT, we found efficient antigen presentation that is reflected in the production of IFN‐γ and IL‐17 by CD4+ T cells over IL‐4 or IL‐5 production. The CTB‐induced activation of DCs in the ear occurred without visible inflammation, which reflects a similar type of CD4+ T‐cell differentiation. In both cases, the elicited response was dependent on the presence of migrating skin cells. Remarkably, immunization with CT or with CTB led to the induction of a delayed‐type hypersensitivity (DTH) response in the ear. The DTH response that was induced by CT immunization was dependent on IL‐17 and partially dependent on IFN‐γ activity. These results indicate that both CT and CTB induce an efficient CD4+ T‐cell response to a co‐administered antigen following ear immunization that is dependent on migrating DCs.
Bcl6: Where too much complexity is barely enough
Authors: Tarlinton David M.
Published: July 2011

Appropriate B‐cell differentiation in response to antigen is fundamental to health. Central to the regulation of this process in circumstances of T‐cell‐dependent immune responses is the transcriptional repressor Bcl6, which is required for germinal centre (GC) formation and function. Within GCs, Bcl6 is already known to regulate many functions including proliferation, assessing DNA damage and terminal differentiation. Targets of Bcl6 repression in B cells have been identified in a variety of systems with some, such as the reciprocal regulation of the Prdm1 gene encoding Blimp1, being particularly well studied and in effect becoming a model for the counter‐regulation of Bcl6 and Blimp1 in a variety of cell types. A study in this issue of the European Journal of Immunology examines the regulatory network of Bcl6 in DT40, a chicken lymphoma, and reproduces some of the complexity of other species but also adds new targets for Bcl6 regulation, genes involved in class switch recombination and somatic hypermutation. While this increasing complexity may be daunting, it emphasises the critical importance of understanding how Bcl6 may integrate the multitude of processes occurring in GCs.
One‐Pot Synthesis of Dual‐Stabilizer‐Capped CdTe Nanocrystals with Efficient Near‐Infrared Photoluminescence and Electrochemiluminescence
Authors: Liang Guo‐dong , Shen Li‐ping , Zhang Xiao‐li , Zou Gui‐zheng
Published: July 2011

CdTe nanocrystals (NCs) are promising near‐infrared (NIR) emitter candidates. A one‐pot synthetic strategy has been developed for high‐quality NIR‐emitting CdTe NCs with mercaptopropionic acid and sodium hexametaphosphate as dual stabilizers. The dual‐stabilizer‐capped CdTe NCs displayed efficient photoluminescence (PL) between the visible and near‐infrared region (533–778 nm) with a quantum yield of up to 47 %. XRD, XPS, and photoluminescence spectra were employed to characterize the structure and optical features of these samples. Moreover, the NIR‐emitting CdTe NCs also displayed strong band‐gap electrochemiluminescence in the NIR region, indicating that this strategy can be used to synthesize NCs with both efficient fluorescence and electrochemiluminescence emissions in the NIR region.
Difference gel electrophoresis identifies differentially expressed proteins in endoscopically collected pancreatic fluid
Authors: Paulo Joao A. , Lee Linda S. , Banks Peter A. , Steen Hanno , Conwell Darwin L.
Published: July 2011

Alterations in the pancreatic fluid proteome of individuals with chronic pancreatitis (CP) may offer insights into the development and progression of the disease. The endoscopic pancreatic function test (ePFT) can safely collect large volumes of pancreatic fluid that are potentially amenable to proteomic analyses using difference gel electrophoresis (DIGE) coupled with liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Pancreatic fluid was collected endoscopically using the ePFT method following secretin stimulation from three individuals with severe CP and three chronic abdominal pain (CAP) controls. The fluid was processed to minimize protein degradation and the protein profiles of each cohort, as determined by DIGE and LC‐MS/MS, were compared. This DIGE‐LC‐MS/MS analysis reveals proteins that are differentially expressed in CP compared with CAP controls. Proteins with higher abundance in pancreatic fluid from CP individuals include: actin, desmoplankin, α‐1‐antitrypsin, SNC73, and serotransferrin. Those of relatively lower abundance include carboxypeptidase B, lipase, α‐1‐antichymotrypsin, α‐2‐macroglobulin, actin‐related protein (Arp2/3) subunit 4, glyceraldehyde‐3‐phosphate dehydrogenase, and protein disulfide isomerase. Endoscopic collection (ePFT) in tandem with DIGE‐LC‐MS/MS is a suitable approach for pancreatic fluid proteome analysis; however, further optimization of our protocol, as outlined herein, may improve proteome coverage in future analyses.
Identification and expansion of a unique stem cell population from adult mouse gallbladder
Authors: Manohar Rohan , Komori Junji , Guzik Lynda , Stolz Donna B. , Chandran Uma R. , LaFramboise William A. , Lagasse Eric
Published: July 2011

The identification of resident stem cells in the mouse gallbladder is, to date, unexplored. In addition, the relationship between adult gallbladder stem cells and intrahepatic bile duct (IHBD) cells is not well understood. The aim of this study was to isolate stem cells from an adult mouse gallbladder and determine whether they were unique, compared to IHBD cells. By limiting dilution analyses and index sorts, we found that an EpCAM+CD49fhi epithelial cell subpopulation from primary gallbladder is enriched in colony-forming cells, compared to EpCAM+CD49flo cells. EpCAM+CD49fhi cells expressed cluster of differentiation (CD)29, CD133, and stem cell antigen-1, but were negative for lineage markers CD31, CD45, and F4/80. Using a novel feeder cell-culture system, we observed long-term (>passage 20) and clonal expansion of the EpCAM+CD49fhi cells in vitro. In a matrigel differentiation assay, EpCAM+CD49f+ cells expanding in vitro underwent organotypic morphogenesis forming ductular structures and cysts. These structures are similar to, and recapitulate a transport function of, primary gallbladder. EpCAM+CD49f+ cells also engraft into the subcutaneous space of recipient mice. We compared primary gallbladder and IHBD cells by flow cytometry and found phenotypic differences in the expression of CD49f, CD49e, CD81, CD26, CD54, and CD166. In addition, oligonucleotide microarrays showed that the expanded EpCAM+CD49f+ gallbladder cells and IHBD cells exhibit differences related to lipid and drug metabolism. Notable genes that were different are cytochrome P450, glutathione S-transferase, Indian hedgehog, and solute carrier family genes. Conclusion: We have isolated an epithelial cell population from primary mouse gallbladder with stem cell characteristics and found it to be unique, compared to IHBD cells. (Hepatology 2011)
Numerical investigation of lobe spacing ratio on performance of forced mixer nozzle
Authors: Xie Yi , Liu You‐hong
Published: July 2011

Geometric models of a lobed mixer nozzle with variation of lobe spacing ratios are created and the corresponding flow fields are simulated using a steady Reynolds Averaged Navier–Stokes (RANS) equation with a realizable k‐ϵ turbulence model and standard wall function. According to the numerical simulation results, the spacing ratio has a large influence on the shape of streamwise vortices, but a relatively small effect on the streamwise vorticity field at the lobe exit. Therefore, at the initial part of mixing, a change of spacing ratio has little effect on the thermal mixing efficiency and the total pressure recovery coefficient. In addition, the thermal mixing efficiency increases sharply at the initial part, and near the nozzle exit it approaches some constant. The development of the total pressure recovery coefficient is totally reverse to the thermal mixing efficiency. It falls rapidly at the beginning. Then the rate of descent gradually slows down, and approaches some constant. At the nozzle exit cross‐section, the thermal mixing efficiency ascends and the total pressure recovery efficiency reduces as the spacing ratio increases. Besides, the thrust coefficient has little relationship to the spacing ratio, with a variation smaller than 0.01 when the spacing ratio increases from 4.87 to 0.497. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20363
Nuclear factor kappa B pathway associated biomarkers in AIDS defining malignancies
Authors: Ramos Juan‐Carlos , Sin Sang‐Hoon , Staudt Michelle R. , Roy Debasmita , Vahrson Wolfgang , Dezube Bruce J. , Harrington William , Dittmer Dirk P.
Published: July 2011

The nuclear factor kappa B (NFκB) pathway is essential for many human cancers. Therapeutics such as bortezomib (Velcade™) that interfere with NFκB signaling are of great clinical interest. NFκB signaling, however, is multifaceted and variable among tissues, developmental and disease entities. Hence, targeted biomarkers of NFκB pathways are of prime importance for clinical research. We developed a novel real‐time qPCR‐based NFκB array. Only mechanistically validated NFκB targets were included. We then used random‐forest classification to define individual genes and gene combinations within the NFκB pathways that define viral lymphoma subclasses as well as Kaposi sarcoma (KS). Few NFκB targets emerged that were universally present in all tumor types tested, underscoring the need for additional tumor‐type specific biomarker discovery. (i) We uncovered tissue of origin‐specific tumor markers, specifically CD69, CSF‐1 and complement factor B (C1QBP) for primary effusion lymphoma (PEL); IL1‐beta, cyclinD3 and CD48 for KS. We found that IL12, jun‐B, msx‐1 and thrombospondin 2 were associated with EBV co‐infection in PEL. (ii) We defined the NFκB signature of Epstein–Barr virus (EBV) positive AIDS‐associated Burkitt lymphoma (BL). This signature identified CCR5 as the key marker. (iii) This signature differed from EBV negative BL consistent with the idea that EBV not only activates NFκB activity but that this virus also reprograms NFκB signaling toward different targets.
Interactive coordination of currently depressed inpatient mothers and their infants during the postpartum period
Authors: Reck Corinna , Noe Daniela , Stefenelli Ulrich , Fuchs Thomas , Cenciotti Francesca , Stehle Eva , Mundt Christoph , Downing George , Tronick Edward Z.
Published: July 2011

In healthy mother–infant dyads, interactions are characterized by a pattern of matching and mismatching interactive states with quick reparation of mismatches into matches. In contrast, dyads in which mothers have postpartum depression show impaired mother–infant interaction patterns over the first few months of the infant's life. The majority of studies that have examined such interaction patterns have drawn on community samples rather than on depressed inpatient samples of mothers who were in a state of current depression at the time of assessment. To date, no study has investigated specific microanalytic patterns of interactive coordination between depressed German mothers and their infants using the Face‐to‐Face Still‐Face paradigm (FFSF). The primary goal of this study was to evaluate specific patterns of dyadic coordination and the capacity for repairing states of miscoordination in an inpatient sample of postpartum currently depressed mothers and their infants as compared with a healthy control group. A sample of 28 depressed inpatient German mothers and their infants (age range = 1–8 months, M age = 4.06 months) and 34 healthy dyads (range = 1–8 months, M age = 3.89 months) were videotaped while engaging in the FFSF. A focus was placed on the play and reunion episodes. Compared with healthy dyads, dyads with depressed mothers showed less coordination of positive matched states and longer latencies when repairing interactive mismatching states into positive matched states. Clinical implications are discussed.
Coralline hydroxyapatite granules inferior to morselized allograft around uncemented porous Ti implants: Unchanged fixation by addition of concentrated autologous bone marrow aspirate
Authors: Baas Jorgen , Svaneby Dea , Jensen Thomas Bo , Elmengaard Brian , Bechtold Joan , Soballe Kjeld
Published: July 2011

We compared early fixation of titanium implants grafted with impacted allograft bone or coralline hydroxyapatite (HA) granules (Pro Osteon 200) with and without the addition of concentrated bone marrow cells (BMC). Autologous bone marrow aspirate was centrifuged to increase the BMC concentration. Four nonloaded cylindrical, porous coated titanium implants with a circumferential gap of 2.3 mm were inserted in the proximal humeri of eight dogs. Coralline HA granules +/− BMC were impacted around the two implants on one side, and allograft +/− BMC was impacted around the contra lateral implants. Observation time was 4 weeks. The implants surrounded by allograft bone had a three‐fold better fixation than the HA‐grafted implants. The concentration of BMC after centrifugation was increased with a factor 2.1. The addition of BMC to either of the bone graft materials had no statistically significant effects on implant fixation. The allografted implants were well osseointegrated, whereas the HA‐grafted implants were largely encapsulated in fibrous tissue. The addition of concentrated autologous BMCs to the graft material had no effect on implant fixation. The HA‐grafted implants were poorly anchored compared with allografted implants, suggesting that coralline HA granules should be considered a bone graft extender rather than a bone graft substitute. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 9–15, 2011.
Cationized bovine serum albumin with pendant RGD groups forms efficient biocoatings for cell adhesion
Authors: Ng Jeck Fei , Weil Tanja , Jaenicke Stephan
Published: July 2011

Cationized bovine serum albumin (cBSA‐147) has been modified by attaching the cyclic pentapeptide cRGDfK to its surface through linkers of different length. Coatings of these bioconjugates on glass surfaces were studied for their ability to stimulate cell adhesion. These chemically modified albumins combine a high number of positive charges which facilitate the initial cell adhesion to the surface with multiple Arg‐Gly‐Asp groups which enable focal adhesion of fibroblast cells by specific interactions with cell‐surface receptors. The biocoatings are easily prepared within a few minutes by simple incubation from a dilute solution of the modified albumin. This constitutes a convenient approach for preparing surfaces for cell adhesion. Excellent focal adhesion of NIH 3T3 fibroblast cells on the biocoatings was observed. About 75% of the seeded cells attached to the cRGDfK‐cBSA‐147 coated surfaces, and 97% of them underwent focal adhesion. Adhering cells were able to grow and proliferate on the coated surfaces, confirming the outstanding biocompatibility of these biocoatings. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Structural, dynamic, and electrostatic properties of fully hydrated DMPC bilayers from molecular dynamics simulations accelerated with graphical processing units (GPUs)
Authors: Ganesan Narayan , Bauer Brad A. , Lucas Timothy R. , Patel Sandeep , Taufer Michela
Published: July 2011

We present results of molecular dynamics simulations of fully hydrated DMPC bilayers performed on graphics processing units (GPUs) using current state‐of‐the‐art non‐polarizable force fields and a local GPU‐enabled molecular dynamics code named FEN ZI. We treat the conditionally convergent electrostatic interaction energy exactly using the particle mesh Ewald method (PME) for solution of Poisson's Equation for the electrostatic potential under periodic boundary conditions. We discuss elements of our implementation of the PME algorithm on GPUs as well as pertinent performance issues. We proceed to show results of simulations of extended lipid bilayer systems using our program, FEN ZI. We performed simulations of DMPC bilayer systems consisting of 17,004, 68,484, and 273,936 atoms in explicit solvent. We present bilayer structural properties (atomic number densities, electron density profiles), deuterium order parameters (SCD), electrostatic properties (dipole potential, water dipole moments), and orientational properties of water. Predicted properties demonstrate excellent agreement with experiment and previous all‐atom molecular dynamics simulations. We observe no statistically significant differences in calculated structural or electrostatic properties for different system sizes, suggesting the small bilayer simulations (less than 100 lipid molecules) provide equivalent representation of structural and electrostatic properties associated with significantly larger systems (over 1000 lipid molecules). We stress that the three system size representations will have differences in other properties such as surface capillary wave dynamics or surface tension related effects that are not probed in the current study. The latter properties are inherently dependent on system size. This contribution suggests the suitability of applying emerging GPU technologies to studies of an important class of biological environments, that of lipid bilayers and their associated integral membrane proteins. We envision that this technology will push the boundaries of fully atomic‐resolution modeling of these biological systems, thus enabling unprecedented exploration of meso‐scale phenomena (mechanisms, kinetics, energetics) with atomic detail at commodity hardware prices. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Heat shock factor 4a (HSF4a) represses HSF2 expression and HSF2‐mediated transcriptional activity
Authors: Kim Soo‐A , Yoon Jung‐Hoon , Ahn Sang‐Gun
Published: July 2011

Heat shock factors (HSFs) are the main transcriptional regulators of the stress‐induced expression of heat shock protein genes. HSF2, which is one of the HSFs, is activated during differentiation and development but it is unclear how they regulate during cellular processes. Here, we examined the role of HSF4a on the regulation of HSF2 in HEK 293 cells. We found that HSF2 levels are negatively correlated with HSF4a expression and that overexpression of HSF4a reduces hemin‐induced HSF2 mRNA and protein levels. Moreover, hemin‐induced activation of HSF2 was also markedly inhibited in HSF4a expressed cells. Immunoprecipitation assay showed that HSF2 binds to the oligomerization domain of HSF4a. Hemin treatment inhibited their interaction and induced localization of HSF2 and HSF4a in nuclear. In addition, we found that HSF4a or HSF4a DNA binding domain (117 aa) inhibited the activity of hemin‐induced HSP70 promoter. Consequently, HSF4a inhibits HSF2 expression or transcriptional activity through negative regulation of HSF2 binding to the HSP70 promoter. In summary, our findings suggest novel mechanisms of HSF2 regulation controlled by HSF4a. J. Cell. Physiol. 227: 1–6, 2012. © 2011 Wiley Periodicals, Inc.
Basigin interacts with both MCT1 and MCT2 in murine spermatozoa
Authors: Mannowetz Nadja , Wandernoth Petra , Wennemuth Gunther
Published: July 2011

Lactate is provided to spermatogenic cells by Sertoli cells as an energy substrate and its transport is regulated by H+‐monocarboxylate co‐transporters (MCTs). In the case of several cell types it is known that MCT1 is associated with basigin and MCT2 with embigin. Here we demonstrate co‐localization and co‐immunoprecipitation of basigin with both MCT1 and MCT2 in sperm, whereas no interaction with embigin was detectable. An investigation of the functional activity of MCT proteins revealed that it was mainly the application of L‐lactate which resulted in a decrease in pHi. The pHi changes were blocked with α‐cyano‐4‐OH cinnamate and the preference for L‐lactate—as opposed to D‐Lactate—was demonstrated by the determination of ATP after exposure to both lactate isomers. We propose that basigin interacts with MCT1 and MCT2 to locate them properly in the membrane of spermatogenic cells and that this may enable sperm to utilize lactate as an energy substrate contributing to cell survival. J. Cell. Physiol. 227: 2154–2162, 2012. © 2011 Wiley Periodicals, Inc.
Perspectives on healthcare reform: A year later, what more do we know?
Authors: Groszkruger Dan
Published: July 2011

PPACA or the Affordable Care Act(1) was signed into law on March 23, 2010.(2) To many, the Affordable Care Act offers the promise of far greater access to high‐quality, affordable care. But to others, PPACA risks unsustainable cost increases, diminished freedoms, and irreparable harm to the world's finest healthcare delivery system. Which characterization will ultimately be proved correct? Or might the actual reforms surprise both proponents and skeptics? With a year of experience under our belts, it seems appropriate to ask: What more do we know about the new law, now?
Back to basics—just how much should a risk manager know about risk financing?
Authors: Miller Vivian B.
Published: July 2011

Whether directly involved in development and implementation of the organization's risk financing program or not, risk management professionals, at the very least, need to be familiar with and understand the various risk financing strategies available to address all areas of exposure. This article addresses the types of coverages and risk financing options that should be considered when developing a comprehensive risk‐financing program, and why it is important for risk management professionals to have some knowledge about these products, in order for their true value to be fully appreciated.