bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and Risk Profiles of Men Detained Under Wisconsin’s Sexually Violent Person Law
Authors: Elwood Richard W. , Doren Dennis M. , Thornton David
Published: December 2008

Previous studies described the characteristics of individuals committed under sexual offender civil commitment laws in Arizona, Florida, and Washington. This study describes the diagnostic and risk profiles of 331 sexual offenders held under Wisconsin’s sexual offender statute and compares them to the people held in those other states. Persons detained under Wisconsin’s law substantially differ from those in the other states. This variability is attributed to differences in both diagnostic procedures and statutory risk thresholds. The authors believe this is the first study to directly compare diagnoses and risk measures of sex offenders referred for commitment in different states, thereby offering a more national view of who is detained under these laws.
Nonoperative Treatment for Osteochondritis Dissecans of the Capitellum
Authors: Mihara Kenichi , Tsutsui Hiroaki , Nishinaka Naoya , Yamaguchi Ken
Published: December 2008

Background

Spontaneous healing potential and progression of osteochondritis dissecans of the capitellum have been unclear.

Hypothesis

Healing potential is high in the early stage of osteochondritis dissecans and low in the advanced stage.

Study Design

Case series; Level of evidence, 4.

Methods

This retrospective study examines 39 patients with osteochondritis dissecans of the capitellum who were treated conservatively. All patients were baseball players (mean age, 12.8 years). After initial examination, all patients were advised to stop heavy use of the elbow. Physical and radiographic examinations were regularly performed and assessed. Mean duration of follow-up was 14.4 months.

Results

Early-stage lesions were present in 30 patients, while 9 patients were diagnosed with advanced lesions. Open capitellar growth plates were observed in 17 patients, and closed capitellar growth plates were seen in 22 patients. On final radiography, 25 of 30 early-stage lesions were assessed as healed. However, only 1 of 9 advanced-stage lesions was assessed as healed. The remaining 8 advanced lesions were unimproved or progressed. Healing of lesions was seen in 16 of 17 patients with an open growth plate and in 11 of 22 patients with a closed growth plate, representing a significant difference between patients with open and closed growth plates (P <. 05).

Conclusion

Spontaneous healing potential of osteochondritis dissecans in early lesions, especially in patients with open capitellar growth plates, appears high, and nonoperative treatment is appropriate. Conversely, healing potential is extremely low in advanced osteochondritis dissecans lesions. Surgical intervention is recommended to achieve lesion healing in advanced cases.
Open Shoulder Repair of Osseous Glenoid Defects
Authors: Wellmann Mathias , Petersen Wolf , Zantop Thore , Herbort Mirco , Kobbe Philipp , Raschke Michael J. , Hurschler Christof
Published: December 2008

Background

To address glenoid bone deficiency, 2 competing surgical approaches are currently recommended: transplantation of a structural bone graft or the coracoid transfer according to Latarjet. Nonetheless, no clear advantages for either procedure are evident.

Hypothesis

The Latarjet procedure will provide an equivalent beneficial effect on glenohumeral stability as the placement of an intra-articular bone graft.

Study Design

Controlled laboratory study.

Methods

Stability testing of 8 cadaveric shoulders was performed in a dynamic shoulder simulator under 4 different conditions: (1) anteroinferior capsulotomy, (2) anteroinferior glenoid defect, (3) transplantation of a contoured bone graft, and (4) Latarjet procedure. Translational movement of the humeral head in response to a load of 25 N was evaluated in the anterior and anteroinferior directions.

Results

The Latarjet procedure significantly reduced translation by 354% relative to the glenoid defect condition at 30° of abduction and by 374% at 60° of abduction. In comparison, the bone graft significantly reduced translation by 179% at 30° of abduction and by 159% at 60° of abduction. The effect of the bone graft was lowest in external rotation at 60° of abduction where a decrease of translation of 133% was observed. Comparing both reconstruction techniques, the Latarjet procedure resulted in significantly less anterior and anteroinferior translation at 60° of abduction.

Conclusion

Biomechanically, the Latarjet procedure outperforms the bone graft in reducing translation in anteroinferior glenoid bone defects. The advantage of the Latarjet procedure is particularly evident at 60° of glenohumeral abduction.

Clinical Relevance

On the basis of the results of this biomechanical study, the authors recommend the Latarjet procedure for restoring stability in shoulders with a significant glenoid bone defect.
Asset Management Data Practices for Supporting Project Selection Decisions
Authors: Pantelias Aristeidis , Flintsch Gerardo W. , Bryant James W. , Chen Chen
Published: December 2008

Transportation agencies engage in extensive data collection activities to support their decision processes at various levels, but not all data collected supply useful information. This article summarizes research aimed at formally identifying links between data collection and the supported decision processes, particularly at the level of project selection. The aim was to help transportation agencies optimize their data collection and cut down data collection and management costs. The methodology included a comprehensive literature review that collected information from various academic and industry sources around the world and the development of a Web survey that was e-mailed to specific expert individuals within the 50 U.S. Departments of Transportation and Puerto Rico. The responses obtained from the Web survey were analyzed statistically and combined with the additional resources to extract conclusions about the current state of the practice and develop data collection recommendations in the form of a proposed stepwise framework.
Incorporating Queers: Blowback, Backlash, and Other Forms of Resistance to Workplace Diversity Initiatives That Support Sexual Minorities
Authors: Hill Robert J.
Published: December 2008

The problem and the solution. The Academy of Human Resource Development's Standards on Ethics and Integrity states that,“HRD professionals accord appropriate respect to the fundamental rights, dignity, and worth of all people.” This article offers insights into the resistance encountered when organizations acknowledge the worth of sexual minorities. Lesbian, gay, bisexual, transgender, and self-identified Queer (LGBTQ) individuals occupy complex and contradictory worlds in organizations, including the workplace. Causes of backlash, also known as blowback, to diversity change in the context of LGBTQ rights and dignity are presented. It lays out evidence-based practices that may help human resource development professionals to avoid resistance that can result from their attempts to transform organizations into fully inclusive places.
An Examination of Current Assessment Practices in Northeastern School Districts
Authors: Madaus Joseph , Rinaldi Claudia , Bigaj Stephen , Chafouleas Sandra M.
Published: December 2008

Despite the central role of assessment in special education, there is a paucity of current research on instruments and methods used in schools. Special education directors ( N = 164) in five northeastern states responded to an electronic survey related to the use of assessment instruments and methods in their districts. Data are presented regarding district decision-making related to instrument selection and purchase as well as professional development for district staff. The specific use of tests in academic, adaptive, intelligence, and content areas are also presented, as is the frequency of use of 11 assessment procedures, including response to intervention. Implications for preservice and in-service training are discussed.
Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression
Authors: Jackson Stephen M. , Harp Natessa , Patel Darshna , Wulf Jordan , Spaeth Erich D. , Dike Uzoamaka K. , James Judith A. , Capra J. Donald
Published: December 2008

We previously reported that RO+ expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD−CD38+ GC B cells, into different fractions based on RB expression. Although each subset contained RB+ cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB+ GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB- and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM+IgD+CD38+CD27−) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgD−CD38++CD27+) and memory (IgD−CD38−CD27+) transition. Interestingly, RB+ GC B cells showed increased signs of terminal differentiation toward CD27+ post-GC early plasmablast (increased CD38 and RO) or early memory (decreased CD38 and RO) B cells. We propose that as in T cells, differential RB expression directly correlates with development- and function-based transitions in tonsillar B cells. Application of this RB:RO system should advance our understanding of normal B-cell development and facilitate the isolation of more discrete B-cell populations with potentially different propensities in disease pathogenesis.
High-affinity neurotrophin receptors and ligands promote leukemogenesis
Authors: Li Zhixiong , Beutel Gernot , Rhein Mathias , Meyer Johann , Koenecke Christian , Neumann Thomas , Yang Min , Krauter Jürgen , von Neuhoff Nils , Heuser Michael , Diedrich Helmut , Göhring Gudrun , Wilkens Ludwig , Schlegelberger Brigitte , Ganser Arnold , Baum Christopher
Published: December 2008

Neurotrophins (NTs) and their receptors play a key role in neurogenesis and survival. The TRK (tropomyosin-related kinase) receptor protein tyrosine kinases (TRKA, TRKB, TRKC) are high-affinity NT receptors that are expressed in a variety of human tissues. Their role in normal and malignant hematopoiesis is poorly understood. In a prospective study involving 94 adult patients we demonstrate for the first time cell-surface expression of the 3 TRKs and constitutive activation in blasts from patients with de novo or secondary acute leukemia. At least one TRK was expressed in 55% of the analyzed cases. We establish a clear correlation between the TRK expression pattern and FAB classification. Although only few point mutations were found in TRK sequences by reverse-transcriptase–polymerase chain reaction (RT-PCR), we observed coexpression of BDNF (ligand for TRKB) in more than 50% of TRKB+ cases (16/30). Activation of TRKA or TRKB by NGF and BDNF, respectively, efficiently rescued murine myeloid cells from irradiation-induced apoptosis. Coexpression of TRKB/BDNF or TRKA/NGF in murine hematopoietic cells induced leukemia. Moreover, activation of TRKs was important for survival of both human and murine leukemic cells. Our findings suggest that TRKs play an important role in leukemogenesis and may serve as a new drug target.
Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors
Authors: Whitecross Kate F. , Alsop Amber E. , Cluse Leonie A. , Wiegmans Adrian , Banks Kellie-Marie , Coomans Claudia , Peart Melissa J. , Newbold Andrea , Lindemann Ralph K. , Johnstone Ricky W.
Published: December 2008

The apoptotic and therapeutic activities of the histone deacetylase inhibitor (HDACi) vorinostat are blocked by overexpresssion of Bcl-2 or Bcl-XL. Herein, we used the small molecule inhibitor ABT-737 to restore sensitivity of Eμ-myc lymphomas overexpressing Bcl-2 or Bcl-XL to vorinostat and valproic acid (VPA). Combining low-dose ABT-737 with vorinostat or VPA resulted in synergistic apoptosis of these cells. ABT-737 was ineffective against Eμ-myc/Mcl-1 and Eμ-myc/A1 cells either as a single agent or in combination with HDACi. However, in contrast to the reported binding specificity data, Eμ-myc/Bcl-w lymphomas were insensitive to ABT-737 used alone or in combination with HDACi, indicating that the regulatory activity of ABT-737 is restricted to Bcl-2 and Bcl-XL. Eμ-myc lymphomas that expressed Bcl-2 throughout the tumorigenesis process were especially sensitive to ABT-737, while those forced to overexpress Mcl-1 were not. This supports the notion that tumor cells “addicted” to ABT-737 target proteins (ie, Bcl-2 or Bcl-XL) are likely to be the most sensitive target cell population. Our studies provide important preclinical data on the binding specificity of ABT-737 and its usefulness against primary hematologic malignancies when used as a single agent and in combination with HDACi.
Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy)
Authors: Riess Hanno , Pelzer Uwe , Hilbig Andreas , Stieler Jens , Opitz Bernhard , Scholten Theo , Kauschat-Brüning Dörte , Bramlage Peter , Dörken Bernd , Oettle Helmut
Published: December 2008

Background

Advanced pancreatic cancer, in addition to its high mortality, is characterized by one of the highest rates of venous thromboembolic events (VTE) as compared to other types of cancer. Enoxaparin, a low molecular weight heparin (LMWH), has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients. Results of some small studies suggest that this benefit might extend to patients with cancer, however, enoxaparin is not currently indicated for this use. This phase IIb study was designed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy.

Methods

The aim of this prospective multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation in 540 patients. Primary endpoint is the incidence of clinically relevant VTE (symptomatic deep venous thrombosis (DVT) of the leg and/or pelvic and/or pulmonary embolism (PE)) within the first 3 months. Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6, 9 and 12 months as well as remission at 3, 6, 9 and 12 months, overall survival and bleeding. Trial registration: isrctn.org identifier CCT-NAPN-16752, controlled-trials.com identifier: ISRCTN02140505.

Results

An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding (5 pts vs. 6 pts, Chi2: 0.763).

Conclusion

PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer. Its results will lead to a new understanding of the role of heparins in the prevention of venous thromboembolism and of their effect on survival, remission rates and toxicity of chemotherapeutic regimens.
Tumor necrosis is associated with increased alphavbeta3integrin expression and poor prognosis in nodular cutaneous melanomas
Authors: Bachmann Ingeborg M , Ladstein Rita G , Straume Oddbjørn , Naumov George N , Akslen Lars A
Published: December 2008

Background

Tumor necrosis and apoptotic activity are considered important in cancer progression, but these features have not been much studied in melanomas. Our hypothesis was that rapid growth in cutaneous melanomas of the vertical growth phase might lead to tissue hypoxia, alterations in apoptotic activity and tumor necrosis. We proposed that these tumor characteristics might be associated with changes in expression of cell adhesion proteins leading to increased invasive capacity and reduced patient survival.

Methods

A well characterized series of nodular melanoma (originally 202 cases) and other benign and malignant melanocytic tumors (109 cases) were examined for the presence of necrosis, apoptotic activity (TUNEL assay), immunohistochemical expression of hypoxia markers (HIF-1 α, CAIX, TNF-α, Apaf-1) and cell adhesion proteins (αvβ3 integrin, CD44/HCAM and osteopontin). We hypothesized that tumor hypoxia and necrosis might be associated with increased invasiveness in melanoma through alterations of tumor cell adhesion proteins.

Results

Necrosis was present in 29% of nodular melanomas and was associated with increased tumor thickness, tumor ulceration, vascular invasion, higher tumor proliferation and apoptotic index, increased expression of αvβ3 integrin and poor patient outcome by multivariate analysis. Tumor cell apoptosis did also correlate with reduced patient survival. Expression of TNF-α and Apaf-1 was significantly associated with tumor thickness, and osteopontin expression correlated with increased tumor cell proliferation (Ki-67).

Conclusion

Tumor necrosis and apoptotic activity are important features of melanoma progression and prognosis, at least partly through alterations in cell adhesion molecules such as increased αvβ3 integrin expression, revealing potentially important targets for new therapeutic approaches to be further explored.
Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells
Authors: Zaytseva Yekaterina Y , Wang Xin , Southard R Chase , Wallis Natalie K , Kilgore Michael W
Published: December 2008

Background

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARγ has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARγ signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both in vitro and in vivo studies are inconsistent and suggest that endogenous activation of PPARγ plays a much more complex role in initiation and progression of cancer than previously thought.

Results

We have previously demonstrated that an increase in expression of PPARγ1 in MCF-7 breast cancer cells is driven by a tumor-specific promoter. Myc-associated zinc finger protein (MAZ) was identified as a transcriptional mediator of PPARγ1 expression in these cells. In this study, using RNA interference (RNAi) to inhibit PPARγ1 expression directly or via down-regulation of MAZ, we report for the first time that a decrease in PPARγ1 expression results in reduced cellular proliferation in MCF-7 breast cancer cells. Furthermore, we demonstrate that these changes in proliferation are associated with a significant decrease in cell transition from G1 to the S phase. Using a dominant-negative mutant of PPARγ1, Δ462, we confirmed that PPARγ1 acts as a pro-survival factor and showed that this phenomenon is not limited to MCF-7 cells. Finally, we demonstrate that down-regulation of PPARγ1 expression leads to an induction of apoptosis in MCF-7 cells, confirmed by analyzing Bcl-2 expression and PARP-1 cleavage.

Conclusion

Thus, these findings suggest that an increase in PPARγ1 signaling observed in breast cancer contributes to an imbalance between proliferation and apoptosis, and may be an important hallmark of breast tumorigenesis. The results presented here also warrant further investigation regarding the use of PPARγ ligands in patients who are predisposed or already diagnosed with breast cancer.
Fatigue characteristics in multiple sclerosis: the North American Research Committee on Multiple Sclerosis (NARCOMS) survey
Authors: Hadjimichael Olympia , Vollmer Timothy , Oleen-Burkey MerriKay
Published: December 2008

Background

Fatigue is a common disabling symptom of multiple sclerosis (MS) and has a significantly negative impact on quality of life. Persons with MS enrolled in the North American Research Committee on Multiple Sclerosis (NARCOMS) Patient Registry are invited to complete follow-up surveys every six months to update their original registration information. One of these surveys was designed to focus on the severity and impact of fatigue, and its association with other clinical parameters of MS such as physical disability.

Methods

In addition to the usual data collected in Registry update surveys such as demographic characteristics, MS-related medical history, disability and handicap, immunomodulatory and symptomatic therapies taken, and healthcare services used, the survey for this study included two validated self-report fatigue scales, the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) and questions about the use of symptomatic management for fatigue, both pharmacologic and non-pharmacologic treatments. This Registry update survey was mailed to all NARCOMS registrants (n = 18,595) in November 2002. Information provided by registry participants was approved for research purposes by the Yale University Institutional Review Board.

Results

The response rate for the survey was 49.5% (9205/18,595). Severe fatigue as measured with the FSS using the developer's recommended severity cutpoint of ≥ 36 was reported by 6691 (74%) of evaluable respondents (n = 9077). A higher prevalence of severe fatigue was observed in relapsing-worsening MS compared with relapsing-stable and primary progressive MS. A distinct pattern of fatigue was observed across the disability levels of the Patient-Determined Disease Steps (PDDS). Although there were no differences in the severity or impact of fatigue by immunomodulatory agents (IMA), respondents who recalled therapy changes in the prior six months reported different patterns of change in fatigue with lower fatigue levels reported after changing from interferon-β to glatiramer acetate than after changing from glatiramer acetate to interferon-β. Concomitant therapy for fatigue was used by 47.2% of the 5799 survey respondents receiving IMA.

Conclusion

Characterizing MS symptoms like fatigue can increase awareness about their impact on persons with MS and suggest recommendations for a care plan.
Modelling phagosomal lipid networks that regulate actin assembly
Authors: Kühnel Mark , Mayorga Luis S , Dandekar Thomas , Thakar Juilee , Schwarz Roland , Anes Elsa , Griffiths Gareth , Reich Jens
Published: December 2008

Background

When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel.

Results

We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds.

In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator). However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box) approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP.

Conclusion

By establishing an active 'dialogue' between an initial complex model and experimental observations, we could narrow the set of differential equations and parameters required to characterize the time-dependent changes of metabolites influencing actin nucleation on phagosomes. For this, the global model was dissected into three sub-models: ATP consumption, lipid interconversion, and nucleation of actin on phagosomal membranes. This scheme allowed us to describe this complex system with a relatively small set of differential equations and kinetic parameters that satisfactorily reproduced the experimental data.
FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease
Authors: Chen Rong , Morgan Alex A , Dudley Joel , Deshpande Tarangini , Li Li , Kodama Keiichi , Chiang Annie P , Butte Atul J
Published: December 2008

Background

Candidate single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) were often selected for validation based on their functional annotation, which was inadequate and biased. We propose to use the more than 200,000 microarray studies in the Gene Expression Omnibus to systematically prioritize candidate SNPs from GWASs.

Results

We analyzed all human microarray studies from the Gene Expression Omnibus, and calculated the observed frequency of differential expression, which we called differential expression ratio, for every human gene. Analysis conducted in a comprehensive list of curated disease genes revealed a positive association between differential expression ratio values and the likelihood of harboring disease-associated variants. By considering highly differentially expressed genes, we were able to rediscover disease genes with 79% specificity and 37% sensitivity. We successfully distinguished true disease genes from false positives in multiple GWASs for multiple diseases. We then derived a list of functionally interpolating SNPs (fitSNPs) to analyze the top seven loci of Wellcome Trust Case Control Consortium type 1 diabetes mellitus GWASs, rediscovered all type 1 diabetes mellitus genes, and predicted a novel gene (KIAA1109) for an unexplained locus 4q27. We suggest that fitSNPs would work equally well for both Mendelian and complex diseases (being more effective for cancer) and proposed candidate genes to sequence for their association with 597 syndromes with unknown molecular basis.

Conclusions

Our study demonstrates that highly differentially expressed genes are more likely to harbor disease-associated DNA variants. FitSNPs can serve as an effective tool to systematically prioritize candidate SNPs from GWASs.
Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell development
Authors: Katebi Majid , Soleimani Mansooreh , Cronstein Bruce N
Published: December 2008

Bone marrow-derived mesenchymal stem cells (BM-MSCs) play a role in wound healing and tissue repair and may also be useful for organ regeneration. As we have demonstrated previously that A2A adenosine receptors (A2AR) promote tissue repair and wound healing by stimulating local repair mechanisms and enhancing accumulation of endothelial progenitor cells, we investigated whether A2AR activation modulates BM-MSC proliferation and differentiation. BM-MSCs were isolated and cultured from A2A-deficient and ecto-5′nucleotidase (CD73)-deficient female mice; the MSCs were identified and quantified by a CFU-fibroblast (CFU-F) assay. Procollagen α2 type I expression was determined by Western blotting and immunocytochemistry. MSC-specific markers were examined in primary cells and third-passage cells by cytofluorography. PCR and real time-PCR were used to quantitate adenosine receptor and CD73 expression. There were significantly fewer CFU-Fs in cultures of BM-MSCs from A2AR knockout (KO) mice or BM-MSCs treated with the A2AR antagonist ZM241385, 1 μM. Similarly, there were significantly fewer procollagen α2 type I-positive MSCs in cultures from A2AR KO and antagonist-treated cultures as well. In late passage cells, there were significantly fewer MSCs from A2A KO mice expressing CD90, CD105, and procollagen type I (P<0.05 for all; n=3). These findings indicate that adenosine and adenosine A2AR play a critical role in promoting the proliferation and differentiation of mouse BM-MSCs.
Impaired Steroidogenesis and Implantation Failure in Bmal1−/− Mice
Authors: Ratajczak Christine K. , Boehle Katie L. , Muglia Louis J.
Published: December 2008

Evidence in humans and rodents suggests that normal circadian rhythmicity is important for supporting reproductive function. A molecular clock underlies circadian rhythmicity. Impaired fertility is observed in some genetically altered mice with deficiencies in genes of the molecular clock, suggesting a critical role for these genes in reproduction. Here we systematically characterize the reproductive phenotype of females deficient in the clock gene Bmal1. Bmal1−/− females are infertile. They exhibit progression through the estrous cycle, although these cycles are prolonged. Normal follicular development occurs in Bmal1−/− females, and healthy embryos of the expected developmental stage are found in the reproductive tract of Bmal1−/− females 3.5 d after mating to wild-type males. However, serum progesterone levels are significantly lower in Bmal1−/−vs. Bmal1+/± females on d 3.5 of gestation. Low progesterone levels in Bmal1−/− females are accompanied by decreased expression of steroidogenic acute regulatory protein in corpora lutea of Bmal1−/−vs. Bmal1+/± females. Whereas implantation of embryos is not observed in untreated or vehicle-treated Bmal1−/− females, exogenous administration of progesterone to Bmal1−/− females is able to reinstitute implantation. These data suggest that implantation failure due to impaired steroidogenesis causes infertility of Bmal1−/− females.
Interaction with Notch determines endocytosis of specific Delta ligands in zebrafish neural tissue
Authors: Matsuda Miho , Chitnis Ajay B.
Published: December 2008

Mind bomb1 (Mib1)-mediated endocytosis of the Notch ligand DeltaD is essential for activation of Notch in a neighboring cell. Although most DeltaD is localized in cytoplasmic puncta in zebrafish neural tissue, it is on the plasma membrane in mib1 mutants because Mib1-mediated endocytosis determines the normal subcellular localization of DeltaD. Knockdown of Notch increases cell surface DeltaA and DeltaD, but not DeltaC, suggesting that,like Mib1, Notch regulates endocytosis of specific ligands. Transplant experiments show that the interaction with Notch, both in the same cell (in cis) and in neighboring cells (in trans), regulates DeltaD endocytosis. Whereas DeltaD endocytosis following interaction in trans activates Notch in a neighboring cell, endocytosis of DeltaD and Notch following an interaction in cis is likely to inhibit Notch signaling by making both unavailable at the cell surface. The transplantation experiments reveal a heterogeneous population of progenitors: in some, cis interactions are more important; in others, trans interactions are more important; and in others, both cis and trans interactions are likely to contribute to DeltaD endocytosis. We suggest that this heterogeneity represents the process by which effective lateral inhibition leads to diversification of progenitors into cells that become specialized to deliver or receive Delta signals, where trans and cis interactions with Notch play differential roles in DeltaD endocytosis.
Coprecipitated Gold–Tricobalt Tetraoxide Catalyst for Heterogeneous Hydroformylation of Olefins
Authors: Liu Xiaohao , Haruta Masatake , Tokunaga Makoto
Published: December 2008

The combination of gold (Au0) and tricobalt tetraoxide (Co3O4) prepared by coprecipitation gives high-performance heterogeneous catalysts for hydroformylation reaction with selectivity above 85% in desired aldehydes, although neither Au0 nor Co3O4 have been demonstrated in this reaction and show poor activities. The Au/Co3O4 catalysts can be recycled by simple decantation with slight decrease in catalytic activity along with recycle times. The role of Au may mainly promote in situ reduction of Co3O4 to Co0 catalyzing the hydroformylation reaction.
Amidocarbonylation of Aldehydes Utilizing Cobalt Oxide-supported Gold Nanoparticles as a Heterogeneous Catalyst
Authors: Hamasaki Akiyuki , Liu Xiaohao , Tokunaga Makoto
Published: December 2008

Cobalt oxide-supported gold-nanoparticles-catalyzed transformation of aldehydes and their equivalents to N-acyl-α-amino acids was achieved. The desired products were obtained in moderate to excellent yields under milder reaction conditions than previous reports employing octacarbonyldicobalt as a catalyst.
Aqua-aminoorganoboron Catalyst: Engineering Single Water Molecule to Act as an Acid Catalyst in Nitro Aldol Reaction
Authors: Yoshimoto Junichi , Sandoval Christian A , Saito Susumu
Published: December 2008

We have disclosed the catalytic potential hidden behind a series of aqua-aminoorganoboron compounds in the formation and reaction of nitronate species. The pivotal role of a single-coordinated water molecule in the catalyst was demonstrated by comparison with the D2O-analogue. The present results provide a new strategy for the design of metal-free catalysts which function via elaborative hydrogen-bonding networks involving water.
Neopentyl-substituted PNP-pincer Ligand: Complexation with Iridium to Form an Iridacycle via Alkyl C–H Activation
Authors: Yano Toshiyuki , Moroe Yoshiki , Yamashita Makoto , Nozaki Kyoko
Published: December 2008

A new PNP-pincer ligand 1 bearing neopentyl substituents reacted with [Ir(cod)2]BF4 to form hydridoiridacycle 3 via oxidative addition of a C–H bond of a neopentyl group to IrI. Addition of π-acceptor ligands induced C–H reductive elimination to form cationic iridium(I) complexes 5 ligated by the π-acceptor ligand. Although 3 did not give a benzene adduct, reaction of 3 with nitrobenzene or acetophenone afforded the C–H activated 7a or 8a.
Quantifying the Economic Value of Warranties in the U.S. Server Market
Authors: Chu Junhong , Chintagunta Pradeep K.
Published: December 2008

We quantify the economic value of hardware base warranties in the U.S. server market to manufacturers, channel intermediaries, and customers. We further decompose the value of a warranty into its insurance value and its price discrimination value, which are the two main rationales for warranty provision in the server market. We use structural modeling and counterfactual experiments to accomplish the empirical task. We derive our demand model from utility maximization, which accounts for a customer's risk aversion behavior and heterogeneity. We obtain our pricing model from the profit maximization behavior of manufacturers and downstream firms in indirect channels, accounting for the institutional realities in the server market. Our empirical analysis uses quarterly data from 1999 to 2004 on server wholesale prices, retail prices, and sales for direct and indirect channels in the U.S. market. We find that manufacturers and downstream firms benefit from warranty provision and from sorting across heterogeneous customers by offering a menu of warranties. Customers also benefit from manufacturer warranty provision as well as from the menu of warranties offered. The insurance value of warranties increases and the price discrimination value of warranties decreases with warranty duration.
Cournot Competition Under Yield Uncertainty: The Case of the U.S. Influenza Vaccine Market
Authors: Deo Sarang , Corbett Charles J.
Published: December 2008

This paper is inspired by the recurring mismatch between demand and supply in the U.S. influenza vaccine market. Economic theory predicts that an oligopolistic market with unregulated but costly entry will experience excess entry and oversupply, not the undersupply observed in the market for influenza vaccine in recent years. In this paper, we examine the interaction between yield uncertainty, a key characteristic of many production processes, including that for influenza vaccine, and firms' strategic behavior. We find that yield uncertainty can contribute to a high degree of concentration in an industry and a reduction in the industry output and the expected consumer surplus in equilibrium. We use parameter values loosely based on the U.S. influenza vaccine market to numerically illustrate the impact of yield uncertainty.
Cross validation issues in multiobjective clustering
Authors: Brusco Michael J. , Steinley Douglas
Published: December 2008

The implementation of multiobjective programming methods in combinatorial data analysis is an emergent area of study with a variety of pragmatic applications in the behavioural sciences. Most notably, multiobjective programming provides a tool for analysts to model trade offs among competing criteria in clustering, seriation, and unidimensional scaling tasks. Although multiobjective programming has considerable promise, the technique can produce numerically appealing results that lack empirical validity. With this issue in mind, the purpose of this paper is to briefly review viable areas of application for multiobjective programming and, more importantly, to outline the importance of cross‐validation when using this method in cluster analysis.
On the modelling and estimation of attribute rankings with ties in the Thurstonian framework
Authors: Poon Wai‐Yin , Xu Liang
Published: December 2008

A Thurstonian type approach is applied to modelling ranking data with ties. It uses a non‐totally differentiable discriminational process instead of the conventional totally differential one to relate the observed rankings and the underlying subjective values. A Monte Carlo expectation–maximization algorithm is proposed to find the maximum likelihood estimates together with the standard errors of the parameters. The approach is examined numerically by means of an artificial example and a simulation study and is applied to a study of attribute assessment.
Discriminating between strong and weak structures in three‐mode principal component analysis
Authors: Ceulemans Eva , Kiers Henk A. L.
Published: December 2008

Recently, a number of model selection heuristics (i.e. DIFFIT, CORCONDIA, the numerical convex hull based heuristic) have been proposed for choosing among Parafac and/or Tucker3 solutions of different complexity for a given three‐way three‐mode data set. Such heuristics are often validated by means of extensive simulation studies. However, these simulation studies are unrealistic in that it is assumed that the variance in real three‐way data can be split into two parts: structural variance, due to a true underlying Parafac or Tucker3 model of low complexity, and random noise. In this paper, we start from the much more reasonable assumption that the variance in any real three‐way data set is due to three different sources: (1) a strong Parafac or Tucker3 structure of low complexity, accounting for a considerable amount of variance, (2) a weak Tucker3 structure, capturing less prominent data aspects, and (3) random noise. As such, Parafac and Tucker3 simulation studies are run in which the data are generated by adding a weak Tucker3 structure to a strong Parafac or Tucker3 one and perturbing the resulting data with random noise. The design of these studies is based on the reanalysis of real data sets. In these studies, the performance of the numerical convex hull based model selection method is evaluated with respect to its capability of discriminating strong from weak underlying structures. The results show that in about two‐thirds of the simulated cases, the hull heuristic yields a model of the same complexity as the strong underlying structure and thus succeeds in disentangling strong and weak underlying structures. In the vast majority of the remaining third, this heuristic selects a solution that combines the strong structure and (part of) the weak structure.
The psychological mindedness assessment procedure – validation study of a Dutch version
Authors: Smith Annemarie J. M. , Kleijn Wim Chr. , Trijsburg Wim R. , Segaar Jaap A. , van der Staak Cees P. F. , Hutschemaekers Giel J. M.
Published: December 2008

Objective The Psychological Mindedness Assessment Procedure [PMAP; McCallum, M. & Piper, W. E. (1990)] operationalizes psychological mindedness as a participant's understanding of the problem presented by two videotaped enacted patients. To possibly enhance predictive power for psychotherapy outcome, we added two video scenarios with emotionally high‐impact. This article describes psychometric properties of the Dutch translation of the PMAP and the extended version, the PMAP‐plus.

Design A therapy‐analogue study with non‐clinical participants (N=100).

Methods In individual sessions, participants watched the four video‐scenarios and responded to the PMAP‐question ‘What seems to be troubling this woman?’. Emotional reactions were measured using the Positive And Negative Affect Schedule [PANAS; Watson, D., Clark, L. E. & Tellegen, A. (1988)].

Results The PMAP and the PMAP‐plus had good interrater reliability. As expected, PMAP‐levels were lower for the newly added high‐emotional scenarios. Validity was further supported by a negative relation of PMAP‐scores with the Negative Affect subscale.

Conclusions The Dutch translation of the PMAP and the added scenarios of the PMAP‐plus are reliable instruments. The predictive power for psychotherapy outcome needs to be investigated in a patient group. The variation in presented clinical problems could also make it a useful instrument to assess psychological mindedness in psychotherapists.
Thirty years on – a large anti‐Flynn effect/ (II): 13‐ and 14‐year‐olds. Piagetian tests of formal operations norms 1976–2006/7
Authors: Shayer Michael , Ginsburg Denise
Published: December 2008

Background Shayer, Ginsburg, and Coe (2007) showed that children leaving primary school in Y6 entered secondary school with much lower levels of understanding of the physical conservations than in 1976. It seemed desirable to investigate cognitive development in the first three years of secondary education.

Aims By using two Piagetian tests of formal operations, one of which had been used in the 1976 CSMS survey, the performance of Y8 and Y9 pupils would be compared with the survey results published in 1978.

Sample Eight schools were selected as willing to test their Y9 or Y8 classes on either the Pendulum (in 2007) or the Equilibrium in the Balance tests (in 2006), giving 39 classes on which to make the comparison with 1976 performance.

Method Regression of the pupils' class mean on each formal test on either the class's 2004 MidYIS or nferCAT standardized scores, and computing the regression at IQ = 100 allows comparison with that found in 1976.

Results On Equilibrium in the Balance the Y8 pupils were down on the proportion at the early formal level or above by −0.61 standard deviations (SD) for boys and −0.63 SD for girls on the 1976 results. On the Pendulum the Y9 boys were down by −0.49 SD and the girls by −0.48 SD on the proportion at the early formal level or above.

Conclusion The negative Flynn‐effect found on Volume & Heaviness for Y7 pupils is paralleled by a similar negative effect on attainment of formal operations by Y8 and Y9, compared with 1976. Yet at the same time the proportion of pupils using the top level of concrete operational thinking has increased on both tests. It seems that there has been a change either in general societal pressures on the individual or in the style of teaching in schools – or both – favouring a lower level of processing of reality.
A Life in the Field: Henry Glassie and the Study of Material Culture
Authors: Glassie Henry , Truesdell Barbara
Published: December 2008

Henry Glassie discusses the early life influences that led him to folklore as his vocation. He describes his formal education; his mentoring by Fred B. Kniffen, whose training shaped Glassie's study of material culture; his job as the state folklorist of Pennsylvania; and his participation in the evolution of public sector folklore. Glassie also describes the centrality of fieldwork to his career, his writings, his teaching, his museum work, and to the folklore enterprise. Finally, he evaluates the earmarks of a successful public history venture and the influence of his work's intention to democratize history.
Differential Recovery of Neural Stem Cells in the Subventricular Zone and Dentate Gyrus After Ionizing Radiation
Authors: Hellström Nina A.K. , Björk-Eriksson Thomas , Blomgren Klas , Kuhn H. Georg
Published: December 2008

Radiation therapy is a widely used treatment for malignant central nervous system tumors. Mature neurons are terminally differentiated, whereas stem and progenitor cells have a prominent proliferative capacity and are therefore highly vulnerable to irradiation. Our aim was to investigate how cranial radiation in young rats would affect stem/progenitor cells in the two niches of adult neurogenesis, the subventricular zone (SVZ) and the dentate gyrus of the hippocampal formation. Nine weeks after irradiation we found that in irradiated animals, hippocampal neurogenesis was reduced to 5% of control levels. Similarly, the numbers of actively proliferating cells and radial glia-like stem cells (nestin+/glial fibrillary acidic protein [GFAP]+) in the dentate gyrus were reduced to 10% and 15% of control levels, respectively. In the irradiated olfactory bulb, neurogenesis was reduced to 40% of control levels, and the number of actively proliferating cells in the SVZ was reduced to 53% of control levels. However, the number of nestin+/GFAP+ cells in the SVZ was unchanged compared with controls. To evaluate the immediate response to the radiation injury, we quantified the amount of proliferation in the SVZ and dentate gyrus 1 day after irradiation. We found an equal reduction in proliferating cells both in dentate gyrus and SVZ. In summary, we show an initial response to radiation injury that is similar in both brain stem cell niches. However, the long-term effects on stem cells and neurogenesis in these two areas differ significantly: the dentate gyrus is severely affected long-term, whereas the SVZ appears to recover with time.
Prospective Isolation of Bronchiolar Stem Cells Based Upon Immunophenotypic and Autofluorescence Characteristics
Authors: Teisanu Roxana M. , Lagasse Eric , Whitesides John F. , Stripp Barry R.
Published: December 2008

Bronchiolar stem cells have been functionally defined in vivo on the basis of their resistance to chemical (naphthalene) injury, their infrequent proliferation relative to other progenitor cell types, and their coexpression of the airway and alveolar secretory cell markers Clara cell secretory protein and pro-surfactant protein C, respectively. Cell surface markers that have previously been used for their prospective isolation included Sca-1 and CD34. Using transgenic animal models associated with stem cell expansion, ablation, and lineage tracing, we demonstrate that CD34pos cells do not belong to the airway epithelial lineage and that cell surface Sca-1 immunoreactivity does not distinguish between bronchiolar stem and facultative transit-amplifying (Clara) cell populations. Furthermore, we show that high autofluorescence (AFhigh) is a distinguishing characteristic of Clara cells allowing for the fractionation of AFlow bronchiolar stem cells. On the basis of these data we show that the defining phenotype of the bronchiolar stem cell is CD45neg CD31neg CD34neg Sca-llow AFlow. This refinement in the definition of bronchiolar stem cells provides a critical tool by which to assess functional and molecular distinctions between bronchiolar stem cells and the more abundant pool of facultative transit-amplifying (Clara) cells.