bluuebunny/crossref_metadata_2025 huggingface dataset:
Model‐free feedback design for a mixed cancer therapy
Authors: Chareyron S. , Alamir M.
Published: March 2009

In this article, a model‐free feedback control design is proposed for the drug administration in mixed cancer therapy. This strategy is very attractive because of the important issue of parameter uncertainties unavoidable when dealing with biological models. The proposed feedback scheme use past measurements to update an on‐line simplified model. The control design is then based on model predictive control in which a suitable switching is performed between two different cost functions. The effectiveness of the proposed model‐free control strategy is validated using a recently developed model (unknown to the controller) governing the cancer growth on a cells population level under combined immune and chemotherapy and using real human data. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Plant‐produced human growth hormone shows biological activity in a rat model
Authors: Rabindran Shailaja , Stevenson Natalie , Roy Gourgopal , Fedorkin Oleg , Skarjinskaia Marina , Ensley Burt , Yusibov Vidadi
Published: March 2009

Plants have been shown to be efficient systems for expressing a wide range of recombinant proteins from various origins. Here, using a plant virus‐based expression vector to produce human growth hormone (hGH) in Nicotiana benthamiana plants, we demonstrate, for the first time, that the plant‐produced hGH (pphGH) is biologically active in a hypophysectomized rat model. We observed an average weight gain of ∼17 g per animal in a group of 10 animals that were injected subcutaneously with pphGH with 60 μg/dose for 10 days. With the increasing demand for hGH, accompanied with the need to make this recombinant protein available to a wider population at a more reasonable cost, plants provide a feasible alternative to current production platforms. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Presenting implicit relevance feedback in educational search engine
Authors: Gao Kai
Published: March 2009

The retrieval result of search engine depends on the proposed query term. If users cannot present proper query terms, some retrieval results are irrelevant. However, it is also difficult for users to present proper terms all the time. Generally, users want to obtain related information including some relevant results rather than those containing given terms merely, so it is necessary for the search engine system to present some relevant results, which can be attained by adopting relevance feedback mechanisms. This article presents some strategies on presenting implicit feedbacks in educational search engine by analyzing clickthrough data and extracting Chinese key‐terms from the relevant pages. In order to do so, users' query statements should be analyzed, and a novel algorithm FPR is used to mine the interests of the majority by analyzing the clickthrough data. The method on Chinese key‐terms weighting and extracting is also present. On the basis of the above works, the proposed educational search engine can feedback some relevant terms. This can present hints for the user to retrieve some relevant results easily. The performance evaluation and experimental results show the feasibility of the approach. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 19: 294–304, 2011
Attributes of social and human capital disclosure and information asymmetry between managers and investors
Authors: Cormier Denis , Aerts Walter , Ledoux Marie‐Josée , Magnan Michel
Published: March 2009

We extend the literature on voluntary disclosure by investigating the impact of precision attribute of social and human capital disclosure on information asymmetry. We provide evidence on how the stock market reacts to different levels of information precision. Overall, results suggest that quantitative disclosure reduces share price volatility and increases Tobin's Q. As expected, firm size attenuates the impact of precision attribute of disclosure on information asymmetry. Furthermore, it appears that firms take into account ultimate costs and benefits to shareholders when determining precision attribute of their disclosure. Finally, our results suggest that efficient governance leads to more disclosure. Copyright © 2009 ASAC. Published by John Wiley & Sons, Ltd.
Workplace risks and stressors as predictors of burnout: The moderating impact of job control and team efficacy
Authors: Day Arla L. , Sibley Aaron , Scott Natasha , Tallon John M. , Ackroyd‐Stolarz Stacy
Published: March 2009

Air medical healthcare (AMH) professionals care for critically‐ill individuals while conveying them to healthcare centres from distant, and frequently dangerous, locations. AMH professionals experience additional health and safety issues beyond the “typical” stressors faced by other healthcare professionals. Therefore, we integrated the safety and psychosocial health literatures to examine the relationship between workplace stressors (risk perception, worries, and patient‐care barriers) and two components of burnout (emotional exhaustion; depersonalization), and the moderating impact of job control and team efficacy for 106 Canadian AMH professionals. Worries over medical hassles and barriers to patient care uniquely predicted emotional exhaustion. Lack of perceived control over one's job was related to exhaustion and depersonalization after controlling for stressors. Job control and team efficacy buffered some of the stressor‐burnout relationships. Copyright © 2009 ASAC. Published by John Wiley & Sons, Ltd.
Measurements of local flow structures of conical spouted beds by optical fibre probes
Authors: Wang Zhiguo , Bi Hsiaotao T. , Lim C. Jim
Published: March 2009

A new calibration set‐up was designed and assembled, and a comprehensive sensitivity analysis was conducted to investigate factors that may affect the calibration of the effective distance of an optical fibre particle velocity probe. It is shown that the glass window has the most significant impact on the calibration result.

The optical fibre probe was then applied to measure local particle velocities and solid fractions inside a half and a full circular conical spouted bed. It is found that the overall particle velocity profiles, as well as the shapes of the spout and fountain are quite similar in both columns.
Investigation of acoustic signals as a tool for characterizing spouted bed dynamics
Authors: Oliveira W.P. , Grace J.R. , Lim C.J. , Hodgson M.R.
Published: March 2009

The feasibility of characterizing the dynamics of a spouted bed based on acoustic emission (AE) signals is evaluated. Acoustic emission signals were measured in a semi‐cylindrical Plexiglas column of diameter 150 mm and height 1000 mm with a conical base of internal angle 60° and 25 mm inlet orifice diameter. Data were obtained for U/Ums from 0.3 to 2.0, static bed height from 250 to 500 mm, and glass beads of diameter 1.2 and 2.4 mm. AE signals reflected the effects of particle size and U/Ums, but in general were insensitive to bed depth, even when there were drastic changes in spouting flow patterns. The results indicate that the AE signals were insensitive to the spouted bed hydrodynamics for the conditions studied. Overall, it appears that the AE analysis is unlikely to be a suitable technique for discriminating spouted bed flow regimes, at least for the range of frequencies and operating conditions investigated.
Determinants and Prognostic Implications of Reperfusion Injury During Primary Percutaneous Coronary Intervention in Chinese Patients with Acute Myocardial Infarction
Authors: Luo Yi , Li Guang‐Lian , Pan Yi‐Zhi , Zhou Shu‐Feng
Published: March 2009

Background

The poor clinical outcome in acute myocardial infarction (AMI) patients undergoing primary percutaneous coronary intervention (PCI) has been attributed to myocardial ischemia‐reperfusion injury (MIRI).

Objective

This study aimed to identify the predictive factors of MIRI during PCI in Chinese AMI patients with or without ST‐segment elevation.

Methods

Clinical and angiographic data of 228 patients in whom the infarct‐related artery (IRA) was successfully recanalized by primary PCI were retrospectively analyzed. Multiple logistic regressions were used.

Results

Compared with non‐MIRI group (n = 109), patients with MIRI (n = 119) were characterized by more inferior infarct location, shorter ischemic duration, more frequently right coronary artery as IRA, more lesion vessels, more often thrombolysis in myocardial infarction (TIMI) 0 flow in IRA prior to PCI, less preinfarction angina, and more renal insufficiency. Ischemic time ≤ 6 hours (p = 0.014), inferior infarct location (p = 0.006), and initial antegrade flow in IRA ≤ TIMI grade 1 (p = 0.028) were independent risk factors for MIRI. Other risk factors included multivessel lesions (p = 0.063) and renal insufficiency (p = 0.067). Only preinfarction angina was a protective factor (p = 0.005).

Conclusions

The factors promoting MIRI during primary PCI includes short ischemic time from AMI onset to IRA recanalization, inferior infarct location, low IRA antegrade flow prior to PCI, multivessel lesions, and renal insufficiency, whereas preinfarction angina is a protective factor attenuating MIRI. Copyright © 2009 Wiley Periodicals, Inc.
Structure‐Based Optimization of Aldose Reductase Inhibitors Originating from Virtual Screening
Authors: Eisenmann Michael , Steuber Holger , Zentgraf Matthias , Altenkämper Mirko , Ortmann Regina , Perruchon Johann , Klebe Gerhard , Schlitzer Martin
Published: March 2009

Virtual screeningdiscovered two prospective hits as potential leads for aldose reductase inhibition. Based on their crystal structures with the enzyme, a systematic optimization has been performed to reveal a first structure–activity relationship. A central thiophen moiety and a terminal nitro group exhibit the best binding properties.

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Diabetes mellitus is a universal health problem. The World Health Organization (WHO) estimates that 150 million people suffer from diabetes mellitus worldwide in 2005. Long‐term complications are a serious problem in the treatment of diabetes, manifesting in macrovascular and microvascular complications. Sorbitol accumulation has been proposed to be an important factor in the development of microvascular complications such as nephropathy, neuropathy, retinopathy or cataract. Catalyzing the NADPH‐dependent reduction of glucose to sorbitol, aldose reductase (ALR2) is an important target in the prevention of these complications. The development of novel aldose reductase inhibitors is expected to benefit strongly from a structure‐based design approach. A virtual screening based on the ultrahigh‐resolution crystal structure of the inhibitor IDD 594 in complex with human ALR2 identified two compounds with IC50values in the low micro‐ to submicromolar range. Based on the known interactions between the ligands and their binding pocket, we simplified the lead structures to give the minimal structural requirements and developed synthetic pathways from commercially available compounds. The newly synthesized compounds were assayed for their inhibition of ALR2, showing inhibitory activities down to the nanomolar range. Crystal structure analysis of the most potent derivative of our series revealed insights into the binding mode of the inhibitors.
The intratumoral distribution of nuclear β‐catenin is a prognostic marker in colon cancer
Authors: Horst David , Reu Simone , Kriegl Lydia , Engel Jutta , Kirchner Thomas , Jung Andreas
Published: March 2009

BACKGROUND:

Most colon cancers harbor mutations of APC or β‐catenin, both of which may lead to nuclear β‐catenin accumulation in the tumor cells and constitutively activated expression of its target genes. In many colon cancers, however, nuclear β‐catenin accumulation is heterogeneous throughout the tumor and often confined to the tumor margin. Herein, the authors investigated whether the intratumoral distribution of nuclear β‐catenin can serve as a prognostic marker for survival and tumor progression of stage IIA colon cancer patients.

METHODS:

In total, 142 patients with primarily resected, moderately differentiated stage IIA colon cancer were included in this study. The patterning of nuclear β‐catenin expression was evaluated on immunohistochemically stained whole tissue sections of the tumors and was correlated with cancer‐specific survival and disease‐free survival using univariate and multivariate statistical analyses.

RESULTS:

Four distinct patterns of nuclear β‐catenin expression were identified, and 2 main categories comprising tumors with or without intratumoral regulation of nuclear β‐catenin were distinguished. Moreover, the results demonstrated that the patterning, and especially the regulation or absence of regulation of nuclear β‐catenin expression, was a strong predictive marker of patient survival and tumor progression.

CONCLUSIONS:

The current results indicated that the distribution of nuclear β‐catenin expression can be used as a good prognostic marker in patients with stage IIA colon cancer. Thus, the evaluation of nuclear β‐catenin may help to identify patients who will have a shorter than average survival and patients with a greater risk of disease progression who may be considered for adjuvant therapeutic modalities and intensified clinical aftercare in the future. Cancer 2009. © 2009 American Cancer Society.
Overlapping functions of Cdx1, Cdx2, and Cdx4 in the development of the amphibian Xenopus tropicalis
Authors: Faas Laura , Isaacs Harry V.
Published: March 2009

Using Xenopus tropicalis, we present the first analysis of the developmental effects that result from knocking down the function of the three Cdx genes present in the typical vertebrate genome. Knockdowns of individual Cdx genes lead to a similar range of posterior defects; compound Cdx knockdowns result in increasingly severe posterior truncations, accompanied by posterior shifts and reduction of 5′ Hox gene expression. We provide evidence that Cdx and Wnt3A genes are components of a positive feedback loop operating in the posterior axis. We show that Cdx function is required during later, but not early stages of development, for correct regional specification of the endoderm and morphogenesis of the gut. Our results support the hypothesis that during amphibian development the overall landscape of Cdx activity in the embryo is more important than the specific function of individual Cdx proteins. Developmental Dynamics 238:835–852, 2009. © 2009 Wiley‐Liss, Inc.
A distinct profile of myogenic regulatory factor detection within Pax7+ cells at S phase supports a unique role of Myf5 during posthatch chicken myogenesis
Authors: Day Kenneth , Paterson Bruce , Yablonka‐Reuveni Zipora
Published: March 2009

Satellite cells are skeletal muscle stem cells that provide myogenic progeny for myofiber growth and repair. Temporal expression of muscle regulatory factors (MRFs) and the paired box transcription factor Pax7 defines characteristic phases of proliferation (Pax7+/MyoD+/myogenin−) and differentiation (Pax7−/MyoD+/myogenin+) during myogenesis of satellite cells. Here, using bromodeoxyuridine (BrdU) labeling and triple immunodetection, we analyzed expression patterns of Pax7 and the MRFs MyoD, Myf5, or myogenin within S phase myoblasts prepared from posthatch chicken muscle. Essentially, all BrdU incorporation was restricted to Pax7+ cells, of which the majority also expressed MyoD. The presence of a minor BrdU+/Pax7+/myogenin+ population in proliferation stage cultures suggests that myogenin up‐regulation is alone insufficient for terminal differentiation. Myf5 was detected strictly within Pax7+ cells and decreased during S phase while MyoD presence persisted in cycling cells. This study provides novel data in support of a unique role for Myf5 during posthatch myogenesis. Developmental Dynamics 238:1001–1009, 2009. © 2009 Wiley‐Liss, Inc.
The characterization of a zebrafish mid‐hindbrain mutant, mid‐hindbrain gone (mgo)
Authors: Shima Takaki , Znosko Wade , Tsang Michael
Published: March 2009

The vertebrate mid‐hindbrain boundary (MHB) is a crucial morphological structure required for patterning and neural differentiation of the midbrain and anterior hindbrain. We isolated a novel zebrafish mutant, MHB gone (mgo), that exhibited a defective MHB. Expression of engrailed3 in the prospective MHB was absent at the 1‐somite stage, suggesting that initiation of the isthmic organizer was disrupted in mgo mutants. Complementation test with mgo and noi, in which the pax2a gene is mutated, infer that the mgo mutant may represent a novel noi allele. However, pronephric, otic vesicle, and commissural axonal defects described in noi mutants were not associated with mgo mutants. Genetic mapping revealed that the mgo mutation is linked to the Pax2a locus, but no mutation was detected in pax2a exons or within intron‐exon boundaries. Based on these findings, we propose that the mgo mutation genetically interacts with pax2a required for the initiation of MHB formation. Developmental Dynamics 238:899–907, 2009. © 2009 Wiley‐Liss, Inc.
Impaired lactation in mice expressing dominant‐negative FADD in mammary epithelium
Authors: Shackleton Mark , O'Reilly Lorraine A. , Sutherland Kate D. , Bath Mary L. , Ellis Sarah , Strasser Andreas , Visvader Jane E. , Lindeman Geoffrey J.
Published: March 2009

The Fas‐associated death domain (FADD/Mort1) adaptor protein was originally identified as a key mediator of apoptosis, although pleiotropic functions for FADD have also been reported. FADD‐mediated tumoricidal effects have been described in breast cancer cells; however, its physiological role in normal mammary gland epithelium is not well understood. To determine the role of FADD signaling during mammary gland development, we generated transgenic mice overexpressing dominant‐negative FADD (DN‐FADD) in mammary epithelium, using the steroid responsive mouse mammary tumor virus promoter. Transgenic mice exhibited a perturbation in lactation resulting in impaired milk production and pup growth retardation. Reduced expansion of alveoli was evident during early lactation with extensive shedding of luminal alveolar cells. Significantly more TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridinetriphosphate nick end‐labeling)‐positive cells were present at this time point and a subsequent increase in bromodeoxyuridine‐positive cells was observed. These findings suggest a role for FADD in maintaining the survival of mammary secretory alveolar cells after the establishment of lactation. Developmental Dynamics 238:1010–1016, 2009. © 2009 Wiley‐Liss, Inc.
In vitro embryo culture in defined, sub‐microliter volumes
Authors: Melin Jessica , Lee Alan , Foygel Kira , Leong Denise E. , Quake Stephen R. , Yao Mylene W.M.
Published: March 2009

The high attrition rate of in vitro human embryo culture presents a major obstacle in the treatment of clinical infertility by in vitro fertilization (IVF). Physical and genetic requirements are not well understood for human or mouse preimplantation embryo development. Group culture is an established requirement for optimal embryo development in the mouse model. However, conventional microdrop culture limitations hinder investigations of the effects of physical parameters on in vitro embryo development. We report a microfluidics platform that enables embryo culture in precisely defined, sub‐microliter volumes (5–500 nl) which cannot be investigated using conventional methods. Groups of two embryos per microfluidic well successfully developed to the blastocyst stage, at a rate of over 80%, which is comparable to those cultured in 20‐μl microdrops. This system can be used to dissect physical requirements of in vitro single or group embryo culture, and be made highly parallel to increase experimental throughput. Developmental Dynamics 238:950–955, 2009. © 2009 Wiley‐Liss, Inc.
Formaldehyde‐based whole‐mount in situ hybridization method for planarians
Authors: Pearson Bret J. , Eisenhoffer George T. , Gurley Kyle A. , Rink Jochen C. , Miller Diane E. , Alvarado Alejandro Sánchez
Published: March 2009

Robust, high resolution formaldehyde‐based in situ hybridization method for the interrogation of planarian regeneration. Schmidtea mediterranea specimen after head and tail regeneration labeled by combining immunofluorescence and double fluorescent in situ hybridization. Riboprobes for Smed‐porcn‐1 (gastrovascular system) and Smed‐slit (midline cells) are shown in blue and green, respectively, while mouse anti‐a‐tubulin antibody (brain, ventral nerve chords, pharynx, flame cells) is shown in red/magenta. Images obtained by Sarah Elliott and Kyle Gurley, University of Utah. See Pearson et al., Developmental Dynamics 238:443‐450. Developmental Dynamics, 2009. © 2009 Wiley‐Liss, Inc.
Molecular cloning of a dominant roller mutant and establishment of DNA‐mediated transformation in the nematode Pristionchus pacificus
Authors: Schlager Benjamin , Wang Xiaoyue , Braach Georg , Sommer Ralf J.
Published: March 2009

We report the molecular cloning of a dominant Roller mutant of Pristionchus pacificus, which encodes a cuticle collagen. We use the mutant locus as a marker to develop transgenic technique by generating complex arrays and present flourescent‐protein based transcriptional reporter constructs for P. pacificus. genesis 47:300–304, 2009. © 2009 Wiley‐Liss, Inc.
The Inorganic–Organic Hybrid Compound {[Mn(trien)]2SnS4}·4H2O: Exhibiting a Hitherto Unknown Binding Mode of the [SnS4]4– Tetrahedron
Authors: Pienack Nicole , Näther Christian , Bensch Wolfgang
Published: March 2009

The compound {[Mn(C6H18N4)]2SnS4}·4H2O (C6H18N4 = triethylenetetramine) was obtained under solvothermal conditions. In the structure of the {[Mn(C6H18N4)]2SnS4}∞ chain, two S atoms of the [SnS4]4– anion act in a hitherto never observed μ3 bridging mode that connects the Mn2S2N8 di‐octahedra. The Mn2+ ions are octahedrally coordinated by four N and two S atoms, and two symmetry‐related octahedra share a common S–S edge. Three of the H2O molecules are joined into chains through H‐bonding interactions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Dinuclear Copper(II) Phosphonates Containing Chelating Nitrogen Ligands: Synthesis, Structure, Magnetism and Nuclease Activity
Authors: Chandrasekhar Vadapalli , Senapati Tapas , Clérac Rodolphe
Published: March 2009

The reaction of Cu(ClO4)2·6H2O with RPO3H2 (R = cyclopentyl, isopropyl, trichloromethyl) in the presence of chelating nitrogen ligands bpya or bpy afforded dinuclear copper phosphonates [Cu2(μ2‐C5H9PO3)2(bpya)2(H2O)2] (H2O)4 (1), [Cu2(μ2‐C3H7PO3)2(bpya)2(H2O)2] (H2O)2 (2) and [Cu2(μ2‐CCl3PO3)2(bpy)2(MeOH)2] (H2O) (3) [bpya = 2,2′‐bipyridylamine, bpy = 2,2′‐bipyridine]. The molecular structures of these complexes reveal that they are isostructural and possess two copper centres that are bridged to each other by two isobidentate phosphonate ligands generating an eight‐membered Cu2O4P2 ring. Magnetic studies on 2 reveal antiferromagnetic behaviour at low temperatures. Dinuclear complexes 1–3 were found to be excellent nucleases and can convert supercoiled pBR322 DNA form I into nick form II in only 30 min without the need for any external oxidant through a hydrolytic pathway. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Numerical implementation of the Crank–Nicolson/Adams–Bashforth scheme for the time‐dependent Navier–Stokes equations
Authors: He Yinnian , Li Jian
Published: March 2009

This article considers numerical implementation of the Crank–Nicolson/Adams–Bashforth scheme for the two‐dimensional non‐stationary Navier–Stokes equations. A finite element method is applied for the spatial approximation of the velocity and pressure. The time discretization is based on the Crank–Nicolson scheme for the linear term and the explicit Adams–Bashforth scheme for the nonlinear term. Comparison with other methods, through a series of numerical experiments, shows that this method is almost unconditionally stable and convergent, i.e. stable and convergent when the time step is smaller than a given constant. Copyright © 2009 John Wiley & Sons, Ltd.
Accreditation in the United States: How did we get to where we are?
Authors: Brittingham Barbara
Published: March 2009

Accreditation has a rich history that has shaped its purposes and processes.
A college president's defense of accreditation
Authors: Oden Robert A.
Published: March 2009

Accreditation may be the sole opportunity for all parts of an institution to inquire together and in depth about the totality of their mission.
Valuing health: a new proposal
Authors: Hausman Daniel M.
Published: March 2009

After criticizing existing systems of health measurement for their unargued commitment to evaluating health states in terms of preferences or well‐being, this essay argues that public rather than private values of health states should help guide the allocation of health‐related resources. Private evaluation of health states is relative to a prior individual choice of specific activities and goals, while public evaluation is relative to the whole range of important activities and goals. Public evaluation is concerned with securing a wide range of choices as well as with success given one's choice. A reasonable simplification from the public perspective is to focus on just two features of health states: the subjective feelings attached to health states and the limitations that health states imply on the range of important activities that individuals can pursue. Focusing on just these two dimensions permits the construction of a parsimonious classification of health states with regard to what matters most from the public perspective. This classification, which resembles those in the HALex and the Rosser and Kind Disability and Distress Index, might best be built on top of existing health‐state classifications, by mapping the health states they define to activity‐limitation/feeling pairs.

To assign values to these pairs, I propose relying on deliberative groups to make comparisons among the pairs with respect to the relation ‘is a more serious limitation on the range of objectives and good lives available to members of the population’. A ranking according to this property, is not a preference ranking, because it is not a ranking in terms of everything that matters to individuals.

Working back from the weights attached to the activity‐limitation/feeling pairs, one can impute weights for the health states in other classification systems that were mapped to those pairs. If those weights coincide roughly with current weights, then one legitimizes current weights and provides a vehicle for their public discussion and possible revision. If those weights do not coincide, then one has both an argument for revising current views of the cost effectiveness of treatments and policies and a method to carry out such a revision. Copyright © 2009 John Wiley & Sons, Ltd.
Targeting AKT with the proapoptotic peptide, TAT‐CTMP: A novel strategy for the treatment of human pancreatic adenocarcinoma
Authors: Simon Peter O. , McDunn Jonathan E. , Kashiwagi Hiroyuki , Chang Katherine , Goedegebuure Peter S. , Hotchkiss Richard S. , Hawkins William G.
Published: March 2009

Pancreatic adenocarcinoma carries an ominous prognosis and has little effective treatment. Several studies have demonstrated that the potently antiapoptotic phosphatidyl inositol 3′‐kinase (PI3K)—protein kinase B/AKT pathway is active in pancreas cancer. A recent study identified an endogenous AKT antagonist, carboxyl terminal modulator protein (CTMP). CTMP inhibits the phosphorylation of AKT, preventing full activation of the kinase. We screened several cell permeable peptides from the N‐terminal domain of CTMP (termed TAT‐CTMP1–4) in vitro and found one that caused significant apoptosis in pancreatic adenocarcinoma cell lines. An inactive variant of this peptide was synthesized and used as a negative control. In all cell lines tested, TAT‐CTMP4 induced a dose‐dependent increase in apoptosis as detected by %‐TUNEL positive cells and %‐active caspase‐3 (% active caspase‐3 ranged from 31.2 to 61.9 at the highest dose tested (10 μM). A screening of various cell and tissue types revealed that the proapoptotic activity was highest in pancreatic adenocarcinoma. TAT‐CTMP induced similar levels of active caspase‐3 as several other known inducers of apoptosis: gemcitabine, radiation therapy, wortmannin and recombinant tumor necrosis factor (TNF)‐α. No apoptosis was observed in donor human peripheral blood mononuclear cells (PBMC, p < 0.01). We further showed that TAT‐CTMP4 could augment either gemcitabine chemotherapy or radiation therapy, standard therapies for pancreas cancer. Pancreatic adenocarcinoma xenografts treated with a single dose of TAT‐CTMP4 demonstrated a marked increase in caspase‐3 positive tumor cells when compared with untreated controls. Additionally, pancreatic adenocarcinoma allografts treated with intratumoral TAT‐CTMP and systemic gemcitabine displayed a significantly smaller tumor burden while undergoing treatment than mice in control groups (p < 0.001). These data indicate that inhibiting AKT with CTMP may be of therapeutic benefit in the treatment of pancreatic adenocarcinoma and, when combined with established therapies, may result in an increase in tumor cell death. © 2009 UICC
P21‐activated kinase 5 is overexpressed during colorectal cancer progression and regulates colorectal carcinoma cell adhesion and migration
Authors: Gong Wei , An Zhengwen , Wang Yunling , Pan Xinyan , Fang Weigang , Jiang Bo , Zhang Hongquan
Published: March 2009

P21‐activated kinase 5 (PAK5) is the recently identified member of the group B p21‐activated kinase (PAK) family which are effectors of the small GTPase Cdc42 and Rac1, known to regulate cell motility and activate cell‐survival signaling pathways. However, overexpression of PAK5 has not been associated with any cancers so far. Interestingly, we found that PAK5 was overexpressed in a variety of colorectal carcinoma (CRC) cell lines in a Western‐blotting examination. Therefore, in this study, we aim to examine the PAK5 expression during CRC progression and to answer if PAK5 is involved in malignant progression of CRC. By immunohistochemistry, our results showed that PAK5 expression was increased with CRC progression through the adenoma to carcinoma sequence, with the most significant increases in invasive and metastatic CRCs (p < 0.0001). Furthermore, increased PAK5 expression was also found with the development of CRC from lower Duke's grades to higher ones (p < 0.01). Moreover, PAK5 was also increased from well to poorly differentiated CRCs (p < 0.01). Using gain and loss of function experiments, we found that PAK5 reduced CRC cell adhesion but promoted their migration on collagen type I. Taken together, our study demonstrated that PAK5 expression increased significantly with malignant progression of CRC and that PAK5 might promote CRC metastasis by regulating CRC cell adhesion and migration. © 2009 UICC
Identification and characterization of a novel CXC chemokine in xenograft tumor induced by mas‐overexpressing cells
Authors: Lin Wen‐Zhen , Li Zhou‐Fang , Tsang Sup‐Yin , Lung Lydia K.W. , Wang Da‐Kui , Chan Wood‐Yee , Zhu You‐Kai , Lee Susanna S.T. , Cheung Wing‐Tai
Published: March 2009

Overexpressions of G protein‐coupled receptor (GPCR) with elevated downstream signaling events have been reported in various tumors. However, the cellular mechanism that GPCR overexpression leads to tumor formation is largely unknown. The orphan GPCR mas was originally isolated from a human epidermoid carcinoma. In vivo studies of mas‐overexpressing cells suggested that xenograft tumor formation was positively correlated with the levels of mas expression. Histochemical analysis indicated that xenograft tumor consisted of mas‐transfected and stromal cells. Biochemical analyses revealed that cells overexpressing mas exhibited significantly increased anchorage‐independent growth, whereas there was no significant difference in cell proliferation in comparison with empty vector‐transfected control cells. Expression profiling using mRNA differential display and Northern analysis indicated an elevated expression of GRO and a novel CXC chemokines, tumor‐induced factor (TIF), in mas‐transfected cells and xenograft tumor. Bacterially expressed recombinant TIF was found to act as a neutrophil chemoattractant in a chemotactic assay. These results suggest that mas overexpression enables anchorage‐independent growth of transformed cells, and interplays of secreted chemokines with stromal cells modulate xenograft tumor formation. Importantly, a novel CXC chemokine, TIF, was identified in the xenograft tumor tissues. © 2009 UICC
The role of precollege data in assessing and understanding student engagement in college
Authors: Cole James S. , Kennedy Marianne , Ben‐Avie Michael
Published: March 2009

Obtaining precollege student data, including attitudes, academic performance, past and expected engagement, and family and student characteristics, is important for institutions to gain a better understanding of the first‐year experience.
Design of a multiphase osteochondral scaffold. I. Control of chemical composition
Authors: Lynn Andrew K. , Best Serena M. , Cameron Ruth E. , Harley Brendan A. , Yannas Ioannis V. , Gibson Lorna J. , Bonfield William
Published: March 2009

This is the first in a series of articles that describe the design and development of a family of osteochondral scaffolds based on collagen‐glycosaminoglycan (collagen‐GAG) and calcium phosphate technologies, engineered for the regenerative repair of defects in articular cartilage. The osteochondral scaffolds consist of two layers: a mineralized type I collagen‐GAG scaffold designed to regenerate the underlying subchondral bone and a nonmineralized type II collagen‐GAG scaffold designed to regenerate cartilage. The subsequent articles in this series describe the fabrication and properties of a mineralized scaffold as well as a two‐layer (one mineralized, the other not) osteochondral scaffold for regeneration of the underlying bone and cartilage, respectively. This article describes a technology through which the chemical composition—particularly the calcium phosphate mass fraction—of triple coprecipitated nanocomposites of collagen, glycosaminoglycan, and calcium phosphate can be accurately and reproducibly varied without the need for titrants or other additives. Here, we describe how the mineral:organic ratio can be altered over a range that includes that for articular cartilage (0 wt % mineral) and for bone (75 wt % mineral). This technology achieves the objective of mimicking the composition of two main tissue types found in articular joints, with particular emphasis on the osseous compartment of an osteochondral scaffold. Exclusion of titrants avoids the formation of potentially harmful contaminant phases during freeze‐drying steps crucial for scaffold fabrication, ensuring that the potential for binding growth factors and drugs is maintained. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Measuring the strength of dermal fibroblast attachment to functionalized titanium alloys in vitro
Authors: Pendegrass Catherine J. , Middleton Claire A. , Gordon David , Jacob Josh , Blunn Gordon W.
Published: March 2009

The success of intraosseous transcutaneous amputation prostheses (ITAP) relies on soft tissue attachment to prevent infection which leads to implant failure. Fibronectin (Fn) has been shown to enhance dermal fibroblast attachment in vitro, however measurement of cell attachment strength has been indirect; using cell area and immunolocalization of focal adhesion components. In this study, we have developed a flow apparatus to assess the biophysical strength of cell attachment to biomaterials used in ITAP. We have demonstrated that dermal fibroblast attachment strength increases significantly up to 96 h and that data from direct and indirect methods of assessing cell attachment strength have a significant positive correlation. Additionally, we have used direct and indirect assessment methods to demonstrate that dermal fibroblast attachment strength is significantly greater on fibronectin‐coated titanium alloy compared with uncoated controls at 1, 4, and 24 hours. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Phenotypic changes in proliferation, differentiation, and migration of chondrocytes: 3D in vitro models for joint wound healing
Authors: Tsai Yu‐Hui , Chen Chun‐Wei , Lai Wen‐Fu T. , Tang Ja‐Reng , Deng Win‐Ping , Yeh Shauh‐Der , Chung Andrew , Zuo Chun S. , Bowley John F.
Published: March 2009

We aim to establish a 3D model of cartilage wound healing, and explore the involvement of chondrocytes in its repair. To characterize chondrocyte involvement in wound healing, an in vitro 3D model composed of chondrocyte mixing with either type II/I collagen or type I collagen matrix was established. The “defects” measuring 5 mm in diameter were made on each collagen matrix‐chondrocyte construct to mimic in vivo cartilage defects. The effects of basic fibroblast growth factor (bFGF) on chondrocytes migration and differentiation were studied. The migration and Glucosaminoglycan (GAG) synthesis of chondrocytes in the defect areas were observed by microscopy after Alcian‐blue staining. In the presence of bFGF, GAG expression increased significantly when chondrocytes were cultured in type II/I collagen matrix compared to type I collagen matrix. However, mild GAG accumulation was also found when cells were cultured in either type I or type II/I collagens without bFGF. In a 3D model of cartilage wound healing, bFGF promote chondrocyte proliferation, migration and differentiation in the presence of type II/I collagen matrix, and showed potential to regulate wound healing. These wound healing models may provide feasible methods to explore various drugs prior to human trials. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Pancreatic cancer stem cells and relevance to cancer treatments
Authors: Bednar Filip , Simeone Diane M.
Published: March 2009

Pancreatic cancer continues to be a malignancy with few therapeutic options. The majority of patients that present for an evaluation have locally advanced or metastatic disease that is incurable by surgical approaches. Chemotherapy and radiotherapy resistance of pancreatic adenocarcinomas limits the efficacy of these therapeutic approaches. Recent evidence supports the existence of human pancreatic cancer stem cells, which appear to drive tumor initiation and progression and are particularly resistant to cell death induced by radiation or chemotherapy. Understanding the mechanisms of pancreatic cancer stem cell self‐renewal and resistance to standard therapies may lead to new, more effective therapies to treat this dismal disease. J. Cell. Biochem. 107: 40–45, 2009. © 2009 Wiley‐Liss, Inc.
On set intersection representations of graphs
Authors: Jukna Stasys
Published: March 2009

The intersection dimension of a bipartite graph with respect to a typeLis the smallest numbertfor which it is possible to assign setsAx⊆{1, …,t} of labels to verticesxso that any two verticesxandyfrom different parts are adjacent if and only if |Ax∩Ay|∈L. The weight of such a representation is the sum Σx|Ax| over all verticesx. We exhibit explicit bipartiten×ngraphs whose intersection dimension is (i) at leastn1/|L| with respect to any typeL, (ii) at least$\sqrt{n}$with respect to any type of the formL={k, k+ 1, …}, and (iii) at leastn1/|R| with respect to any type of the formL={k|k modp∈R}, wherepis a prime number. We also show that any intersection representation of a Hadamard graph must have weight aboutn lnn/ln lnn, independent on the used typeL. Finally, we formulate several problems about intersection dimensions of graphs related to some basic open problems in the complexity of boolean functions. © 2009 Wiley Periodicals, Inc. J Graph Theory 61: 55‐75, 2009
Adapted list coloring of planar graphs
Authors: Esperet Louis , Montassier Mickaël , Zhu Xuding
Published: March 2009

Given an edge coloring F of a graph G, a vertex coloring of G is adapted to F if no color appears at the same time on an edge and on its two endpoints. If for some integer k, a graph G is such that given any list assignment L to the vertices of G, with |L(v)|⩾k for all v, and any edge coloring F of G, G admits a coloring c adapted to F where c(v)∈L(v) for all v, then G is said to be adaptably k‐choosable. In this note, we prove that K5‐minor‐free graphs are adaptably 4‐choosable, which implies that planar graphs are adaptably 4‐colorable and answers a question of Hell and Zhu. We also prove that triangle‐free planar graphs are adaptably 3‐choosable and give negative results on planar graphs without 4‐cycle, planar graphs without 5‐cycle, and planar graphs without triangles at distance t, for any t⩾0. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 127–138, 2009
Stem cell‐based cell therapy in neurological diseases: A review
Authors: Kim Seung U. , de Vellis Jean
Published: March 2009

Human neurological disorders such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, multiple sclerosis (MS), stroke, and spinal cord injury are caused by a loss of neurons and glial cells in the brain or spinal cord. Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. However, the paucity of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. In recent years, neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells, mesenchymal stem cells, and neural stem cells, and extensive efforts by investigators to develop stem cell‐based brain transplantation therapies have been carried out. We review here notable experimental and preclinical studies previously published involving stem cell‐based cell and gene therapies for Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, MS, stroke, spinal cord injury, brain tumor, and lysosomal storage diseases and discuss the future prospects for stem cell therapy of neurological disorders in the clinical setting. There are still many obstacles to be overcome before clinical application of cell therapy in neurological disease patients is adopted: 1) it is still uncertain what kind of stem cells would be an ideal source for cellular grafts, and 2) the mechanism by which transplantation of stem cells leads to an enhanced functional recovery and structural reorganization must to be better understood. Steady and solid progress in stem cell research in both basic and preclinical settings should support the hope for development of stem cell‐based cell therapies for neurological diseases. © 2009 Wiley‐Liss, Inc.
High peak capacity separation of peptides through the serial connection of LC shell‐packed columns
Authors: Donato Paola , Dugo Paola , Cacciola Francesco , Dugo Giovanni , Mondello Luigi
Published: March 2009

High peak capacity was obtained for the separation of a HSA tryptic digest through the serial connection of three LC columns packed with shell material (C18, 15 cm×4.6 mm, 2.7 μm particle size). A major benefit of these particles, consisting of a 1.7 μm solid core and a 0.5 μm porous shell, is the small diffusion path, which reduces axial dispersion of solutes and minimizes peak broadening allowing for higher resolving power to be obtained. Increase in the temperature decreases the viscosity and the backpressure on the columns and in this way allowed to couple multiple columns. Single and multicolumn systems were first evaluated for the separation of a standard sample mixture in the isocratic mode; afterwards three columns could be coupled at 60°C, generating more than 90 000 effective plates (200 000 plates/meter) for the separation of HSA in gradient mode on a conventional HPLC instrument. Peak capacity ratios were found in good accordance with the theoretical gain in resolution, i.e. values of 1.37 and 1.67 were measured, when doubling and tripling the length of stationary phases, respectively (the highest measured peak capacity on three coupled columns was 367).
Phosphopeptide enrichment using microscale titanium dioxide solid phase extraction
Authors: Yu Ying‐Qing , Fournier Jennifer , Gilar Martin , Gebler John C.
Published: March 2009

Identification of phosphopeptides by MS is challenging due to their relatively low abundance in proteomic samples and their limited ionization efficiency. Various affinity enrichment methods have been used in the literature. Titanium dioxide SPE devices have been recently proposed as an alternative to immobilized metal affinity chromatography for phosphopeptide enrichment. This study evaluates the TiO2 method using sorbent packed in a 96 well microscale extraction plate operated using a vacuum manifold. The phosphopeptide recovery and enrichment selectivity were investigated at various loading conditions. The effectiveness of organic additives such as dihydroxybenzoic acid derivatives and other nonaliphatic carboxylic acids on enrichment selectivity was examined. The performance of TiO2 was compared to IMAC sorbent. The results suggest that various additives improve the enrichment selectivity by effectively interfering with the acidic peptides binding to TiO2 sorbent. Interaction of phosphopeptides with sorbent is also affected, which leads to overall reduction in phosphopeptide recovery. The new SPE device was successfully utilized for the extraction of phosphopeptides from yeast lysate digest using 2,5‐dihydroxybenzoic acid to minimize the interference from nonphosphorylated peptides.
Effect of separation dimensions on resolution and throughput using very narrow‐range IEF for 2‐DE after solution phase isoelectric fractionation of a complex proteome
Authors: Lee KiBeom , Pi KyungBae
Published: March 2009

This paper describes how the lengths of the first and second dimensions in narrow pH‐range 2‐DE affect the number of detected protein spots, by analysis of human breast carcinoma cell line lysates prefractionated by solution phase IEF. The aim is to maximize throughput while minimizing experimental costs. In this study, systematic evaluation of narrow‐range IPG strip lengths showed that separation distances were very important, with dramatic increases in resolution when longer gels were used. Compared with 7 cm minigels, maximal resolution was obtained using 18 and 24 cm IPG strips. Systematic evaluation of SDS‐PAGE gel length showed a far weaker influence of separation length on resolution in the second dimension compared with that observed for the IEF dimension. There was little benefit in using separation distances greater than 12–15 cm, at least with currently available electrophoresis units. The work shows that regions of the IPG strip not containing any proteins can be excised to fit a smaller gel if prefractionation using IEF in solution has been performed. As expected, larger 2‐DE gel volumes resulting from the use of longer IPG strips and second dimension gels decreased detection sensitivity when equal protein loads were used. However, this effect could be readily eliminated by increasing the loads applied to IPG strips.