bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype pharmacology of lower urinary tract α1‐adrenoceptors
Authors: Nishimune A , Yoshiki H , Uwada J , Anisuzzaman ASM , Umada H , Muramatsu I 
Published: July 2011

α1‐Adrenoceptors are involved in numerous physiological functions, including micturition. However, the pharmacological profile of the α1‐adrenoceptor subtypes remains controversial. Here, we review the literature regarding α1‐adrenoceptors in the lower urinary tract from the standpoint of α1L phenotype pharmacology. Among three α1‐adrenoceptor subtypes (α1A, α1B and α1D), α1a‐adrenoceptor mRNA is the most abundantly transcribed in the prostate, urethra and bladder neck of many species, including humans. In prostate homogenates or membrane preparations, α1A‐adrenoceptors with high affinity for prazosin have been detected as radioligand binding sites. Functional α1‐adrenoceptors in the prostate, urethra and bladder neck have low affinity for prazosin, suggesting the presence of an atypical α1‐adrenoceptor phenotype (designated as α1L). The α1L‐adrenoceptor occurs as a distinct binding entity from the α1A‐adrenoceptor in intact segments of variety of tissues including prostate. Both the α1L‐ and α1A‐adrenoceptors are specifically absent from Adra1A (α1a) gene‐knockout mice. Transfection of α1a‐adrenoceptor cDNA predominantly expresses α1A‐phenotype in several cultured cell lines. However, in CHO cells, such transfection expresses α1L‐ and α1A‐phenotypes. Under intact cell conditions, the α1L‐phenotype is predominant when co‐expressed with the receptor interacting protein, CRELD1α. In summary, recent pharmacological studies reveal that two distinct α1‐adrenoceptor phenotypes (α1A and α1L) originate from a single Adra1A (α1a‐adrenoceptor) gene, but adrenergic contractions in the lower urinary tract are predominantly mediated via the α1L‐adrenoceptor. From the standpoint of phenotype pharmacology, it is likely that phenotype‐based subtypes such as the α1L‐adrenoceptor will become new targets for drug development and pharmacotherapy.LINKED ARTICLE This article is commented on by Ventura, pp. 1223–1225 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01663.x
Autocrine activation of human monocyte/macrophages by monocyte‐derived microparticles and modulation by PPARγ ligands
Authors: Bardelli C , Amoruso A , Federici Canova D , Fresu LG , Balbo P , Neri T , Celi A , Brunelleschi S 
Published: July 2011

BACKGROUND AND PURPOSE Microparticles (MPs), small membrane‐bound particles originating from different cell types during activation or apoptosis, mediate intercellular communication, exert pro‐coagulant activity and affect inflammation and other pathophysiological conditions. Monocyte‐derived MPs have undergone little investigation and, to our knowledge, have never been evaluated for their possible autocrine effects. Therefore, we assessed the ability of monocyte‐derived MPs to stimulate human monocytes and monocyte‐derived macrophages (MDM).EXPERIMENTAL APPROACH MPs were generated from supernatants of human monocytes stimulated by the calcium ionophore A23187 (12 µM), and then characterized. Human monocytes and MDM of healthy donors were isolated by standard procedures. Cells were challenged by MPs or phorbol 12‐myristate 13‐acetate (PMA, used as standard stimulus), in the absence or presence of PPARγ agonists and antagonists. Superoxide anion production (measured spectrophotometrically), cytokine release (elisa), PPARγ protein expression (immunoblotting) and NF‐κB activation (EMSA assay) were evaluated.KEY RESULTS Monocyte‐derived MPs induced, in a concentration‐dependent manner, oxygen radical production, cytokine release and NF‐κB activation in human monocytes and macrophages, with lower effects than PMA. In both cell types, the PPARγ agonists rosiglitazone and 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) inhibited MPs‐induced stimulation and this inhibition was reversed by a PPARγ antagonist. In human monocyte/macrophages, MPs as well as rosiglitazone and 15d‐PGJ2 induced PPARγ protein expression.CONCLUSION AND IMPLICATIONS In human monocyte/macrophages, monocyte‐derived MPs exert an autocrine activation that was modulated by PPARγ ligands, inducing both pro‐inflammatory (superoxide anion production, cytokine release and NF‐κB activation) and anti‐inflammatory (PPARγ expression) effects.
Activated T cells from umbilical cord blood armed with anti‐CD3 × anti‐CD20 bispecific antibody mediate specific cytotoxicity against CD20+ targets with minimal allogeneic reactivity: a strategy for providing antitumor effects after cord blood transplants
Authors: Thakur Archana , Sorenson Carly , Norkina Oxana , Schalk Dana , Ratanatharathorn Voravit , Lum Lawrence G. 
Published: July 2011

BACKGROUND: In this study, we asked whether anti‐CD3–activated T cells (ATCs) from cord blood (CB) could be expanded and targeted to solid tumors or hematologic malignancies for infusions after unrelated CB stem cell transplant and whether cord blood ATCs (CBATCs) could reduce alloresponsiveness.STUDY DESIGN AND METHODS: CB mononuclear cells (MNCs) were activated with anti‐CD3 (20 ng/mL) and expanded for 14 days in interleukin‐2 (100 IU/mL). CBATCs were armed with anti‐CD3 × anti‐CD20 (CD20Bi) or anti‐CD3 × anti‐Her2 (Her2Bi) bispecific antibodies (CBaATCs) and tested for specific cytotoxicity, cytokine secretion, and alloresponsiveness.RESULTS: Our results show the mean expansion of CBATCs to be 37‐fold after 14 days of culture from either frozen (n = 4) or fresh (n = 4) CB units. Cytotoxicity was optimal when CBATCs were armed with 50 ng of CD20Bi/106 cells. Cytotoxicity peaked between Day 8 and Day 10 for both bispecific antibodies. At an effector‐to‐target ratio of 25:1, the mean cytotoxicities of CBATCs armed with Her2Bi or CD20Bi were 40% (n = 4) and 30% (n = 4), respectively. CBaATCs exhibited peak specific interferon‐γ enzyme‐linked immunosorbent spots on Day 10. CBATCs and CBaATCs suppressed responsiveness to alloantigens by 20% to 50% when compared with normal allogeneic peripheral blood MNC response.CONCLUSION: We showed that armed CBATCs mediate specific cytotoxicity, secrete low levels of cytokines and chemokines, and demonstrate attenuated response to alloantigens.
Vitamin K‐dependent coagulation factor deficiency in trauma: a comparative analysis between international normalized ratio and thromboelastography (CME)
Authors: Nascimento Bartolomeu , Al Mahoos Mohammed , Callum Jeannie , Capone Antonio , Pacher Jennifer , Tien Homer , Rizoli Sandro 
Published: July 2011

BACKGROUND: The use of international normalized ratio (INR) to diagnose vitamin K‐dependent coagulation factor (VitK‐CF) deficiency in trauma has limitations (inability to predict bleeding and long turnaround times). Thromboelastography (TEG) assesses the entire coagulation process. With TEG, reaction time (TEG‐R) is used to assess global coagulation factor activity and takes less than 10 minutes. We assessed the ability of TEG‐R to detect VitK‐CF deficiency in trauma, compared to the INR.STUDY DESIGN AND METHODS: A total of 219 trauma patients with INR, TEG, and all VitK‐CF measured at admission were included. Demographics and laboratory tests, drugs, blood transfusions, and severity scores were analyzed. Specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of INR (≥1.3 and ≥1.5) and TEG‐R (>8 min) to diagnose VitK‐CF deficits (≤50%) were calculated. Secondary outcomes included time to INR and TEG results.RESULTS: Overall, TEG‐R performed worse than INR. TEG‐R had a sensitivity of 33% (95% CI, 16%‐55%), specificity of 95% (95% CI, 91%‐98%), PPV of 47% (95% CI, 23%‐72%), and NPV of 92% (95% CI, 87%‐95%). An INR of 1.5 or greater had a sensitivity of 67% (95% CI, 45%‐84%), specificity of 98% (95% CI, 96%‐99.7%), PPV of 84% (95% CI, 60%‐97%), and NPV of 96% (95% CI, 92%‐98%). An INR of 1.3 or greater also had better sensitivity, PPV, and NPV. For patients on warfarin, the times to INR results and TEG completion were 58 (±23) and 92 (±40) minutes (p = 0.07), respectively. TEG‐R was abnormal in only one patient on warfarin.CONCLUSION: Our study suggests that TEG‐R is not superior at identifying VitK‐CF deficiency compared to INR in trauma.
R‐Curve Behavior of 3Y‐TZP at Cryogenic Temperatures
Authors: Xue Weijiang , Xie Zhipeng , Liu Guanwei , Liu Wei , Yi Jian 
Published: July 2011

We reported, for the first time, the R‐curve behavior of zirconia ceramic stabilized with 3 mol% Y2O3 (3Y‐TZP) at cryogenic temperatures down to liquid nitrogen temperature of 77 K, measured using direct indentation method and analyzed together with the Weibull statistical analysis of fracture strength data. The results provided a detailed understanding on the effect of decreasing temperature to the steady‐state fracture toughness K∞ that only the increase in the transformation toughening shielding term ΔKT contributed to the K∞ value at cryogenic temperatures, whereas the intrinsic fracture toughness K0 is independent of temperature. A more pronounced R‐curve behavior unanticipated by the conventional interpretation was found at cryogenic temperatures, which could be of great significance to the concomitant increment of the fracture strength and toughness. Therefore, it is believed that 3Y‐TZP could be one of the most promising materials in cryogenic structural applications.
Mandibular Overdentures Supported by 6‐mm Dental Implants: A 1‐Year Prospective Cohort Study
Authors: Guljé Felix , Raghoebar Gerry M. , Ter Meulen Jan‐Willem P. , Vissink Arjan , Meijer Henny J. A. 
Published: July 2011

ABSTRACTBackground: The extremely resorbed edentulous mandible, with a bone height of 8 mm or less, is still a challenge in implant dentistry. Recently, dental implants of 6 mm in length have been developed.Purpose: The purpose of this 1‐year prospective cohort study was to evaluate treatment outcome of mandibular overdentures supported by four 6‐mm dental implants.Materials and Methods: Twelve edentulous patients with a mandibular height between 6 and 8 mm participated. The patients were treated with an overdenture supported by four 6‐mm OsseoSpeed™ dental implants (Astra Tech AB, Mölndal, Sweden). Clinical and radiographic parameters were evaluated 1 year after completion of the prosthetic treatment. Patients' satisfaction was scored before implant surgery and 1 year after prosthetic treatment.Results: One‐year implant survival rate was 96% (two implants were lost). One patient had a fracture of the mandible in the region of one of the implants 3 weeks after implant surgery. Mean scores for plaque, calculus, gingiva, bleeding, and pocket probing depth were low. Patients' satisfaction was high.Conclusion: One‐year follow‐up data revealed that four 6‐mm dental implants inserted in an extremely resorbed edentulous mandible provided a solid basis for a bar‐retained overdenture.
Long‐Term Clinical, Microbiological, and Radiographic Outcomes of Brånemark™ Implants Installed in Augmented Maxillary Bone for Fixed Full‐Arch Rehabilitation
Authors: De Bruyn Hugo , Bouvry Peter , Collaert Bruno , De Clercq Calix , Persson G. Rutger , Cosyn Jan 
Published: July 2011

ABSTRACTPurpose: The purpose of this study was to document the long‐term outcome of Brånemark implants installed in augmented maxillary bone and to identify parameters that are associated with peri‐implant bone level.Material and Methods: Patients of a periodontal practice who had been referred to a maxillofacial surgeon for iliac crest bone grafting in the atrophic maxilla were retrospectively recruited. Five months following grafting, they received 7–8 turned Brånemark implants. Following submerged healing of another 5 months, implants were uncovered and restorative procedures for fixed rehabilitation were initiated 2–3 months thereafter. The primary outcome variable was bone level defined as the distance from the implant‐abutment interface to the first visible bone‐to‐implant contact. Secondary outcome variables included plaque index, bleeding index, probing depth, and levels of 40 species in subgingival plaque samples as identified by means of checkerboard DNA–DNA hybridization.Results: Nine out of 16 patients (eight females, one male; mean age 59) with 71 implants agreed to come in for evaluation after on average 9 years (SD 4; range 3–13) of function. One implant was deemed mobile at the time of inspection. Clinical conditions were acceptable with 11% of the implants showing pockets ≥ 5 mm. Periodontopathogens were encountered frequently and in high numbers. Clinical parameters and bacterial levels were highly patient dependent. The mean bone level was 2.30 mm (SD 1.53; range 0.00–6.95), with 23% of the implants demonstrating advanced resorption (bone level > 3 mm). Regression analysis showed a significant association of the patient (p < .001) and plaque index (p = .007) with bone level.Conclusions: The long‐term outcome of Brånemark implants installed in iliac crest‐augmented maxillary bone is acceptable; however, advanced peri‐implant bone loss is rather common and indicative of graft resorption. This phenomenon is patient dependent and seems also associated with oral hygiene.
Bone Graft Healing in Reconstruction of Maxillary Atrophy
Authors: Sjöström Mats , Sennerby Lars , Lundgren Stefan 
Published: July 2011

ABSTRACTPurpose: Evaluate correlations between volume change for iliac crest bone grafts in maxillary reconstruction (graft volume change [GVC]) and bone mineral density (BMD), bone volume fraction (BVF), hematologic bone metabolic factors (I), and identify indicators of implant failure (II).Material and Methods: Forty‐six consecutive patients had their edentulous atrophic maxilla reconstructed with free autogenous bone grafts from anterior iliac crest. Endosteal implants were placed 6 months after graft healing. Computer tomography was performed after 3 weeks and 6 months after grafting. Bone biopsies were taken from the internal table of donor site for calculation (BVF), and blood samples were collected. Implant stability was measured at placement with resonance frequency analysis and expressed as implant stability quotient (ISQ). Implant failure was registered.Results: GVC in onlay bone graft was 37%. The BVF in iliac crest biopsies was 32%. Serum‐IGFBP3 differed with 79% of the samples over normal range. Fifteen patients had one or more implant failures prior to loading (early failures). Forty‐two patients were followed for a minimum of 3 years after implant loading and, in addition, 6/42 patients had one or more implants removed during the follow‐up (late failures). GVC correlated to decreased BMD of lumbar vertebrae L2‐L4 (Kruskal–Wallis test, p = .017). No correlation was found between GVC and hematologic factors (Pearson correlation test) or between GVC and BVF (Kruskal–Wallis test). No correlation was found between ISQ and GVC (Pearson correlation test, p = .865). The association between implant failures and the described factors were evaluated, and no significant correlations were found (unconditional logistic regression).Conclusion: Onlay bone grafts decrease 37% during initial healing period, which correlate to BMD of lumbar vertebrae L2‐L4. No other evaluated parameters could explain GVC. The evaluated factors could not explain implant failure.
Reimplantation of Dental Implants following Ligature‐Induced Peri‐Implantitis: A Pilot Study in Dogs
Authors: Levin Liran , Zigdon Hadar , Coelho Paulo G. , Suzuki Marcelo , Machtei Eli E. 
Published: July 2011

ABSTRACTObjectives: This preliminary investigation aimed to evaluate the potential of contaminated implants to reosseointegrate into pristine sites and, in addition, to assess the potential of osseointegration of new implants in peri‐implantitis sockets in a canine model.Methods: All mandibular premolars were bilaterally extracted from two mongrel dogs. Following 12 weeks of healing, two dental implants were inserted on each hemiarch. Forty‐five days following implant placement, a silk ligature secured with cyanoacrylate was placed around the implants' cervical region in order to induce peri‐implantitis. After another 45 days from ligature placement, the implants were mechanically removed using counter rotation with a ratchet and were reimplanted without any decontamination (neither rinsing nor chemical or mechanical cleaning) in adjacent pristine zones. In sites where implants were removed, new, wider‐diameter implants were placed in the infected sockets. Forty‐five days following reimplantation surgery, the dogs were sacrificed; nondecalcified specimens were processed and toluidine blue stained for morphologic and morphometric (bone‐to‐implant contact [BIC]) assessment under an optical microscope.In dog 1 all the implants (both in the pristine and in the infected sites) survived and osseointegrated while in dog 2, six out of eight implants failed to osseointegrate and exfoliated. Overall, the mean BIC of all implants was 51.08% (SD 20.54). The mean BIC for the infected implants placed into pristine sites was 51.48% ± 26.29% (SD) and the mean BIC for the new implants in peri‐implantitis socket was 50.58% ± 14.27% (SD).Conclusions: Within the limitations of this preliminary investigation, especially the small number of animals, osseointegration seems to be achievable both in infected sites and around contaminated implant surfaces.
Alveolar Bone Regeneration around Immediate Implants Using an Injectable nHAC/CSH Loaded with Autogenic Blood‐Acquired Mesenchymal Progenitor Cells: An Experimental Study in the Dog Mandible
Authors: Han Xue , Liu Hongchen , Wang Dongsheng , Su Fang , Zhang Yong , Zhou Wei , Li Shujun , Yang Rui 
Published: July 2011

ABSTRACTBackground: Lack of osseointegration between a dental implant and the walls of the alveolar bone is a common problem in immediate implantation. Injectable tissue‐engineered bone (ITB) may be an effective and minimally invasive solution to the problem. In this study, an injectable bone cement, nHAC/CSH, which consists of nano‐hydroxyapatite/collagen (nHAC) and calcium sulfate hemihydrate (CaSO4.½H2O; CSH) was investigated as a tissue‐engineered scaffold material with blood‐acquired mesenchymal progenitor cells (BMPC) as seeding cells.Purpose: The aim of the study was to assess the new bone formation around immediate dental implants using nHAC/CSH loaded with dog blood‐acquired mesenchymal progenitor cells (dBMPC) in a canine model.Materials and Methods: dBMPC were first isolated from peripheral blood of healthy adult dogs. Alizarin red and oil red O staining were then used to evaluate the potential of dBMPC to differentiate into bi‐lineage mesenchymal tissues in vitro. Four healthy mongrel dogs were used in this study. The alveolar bone defects around immediate implants of dogs were created. Each defect was randomly assigned to one of the following three groups: (1) the ITB group (dBMPC + nHAC/CSH); (2) injectable bone cement nHAC/CSH; or (3) no materials (controls). Methylene blue staining was used to examine the bone formation after 3 months.Results: Studies in vitro revealed that dBMPC could be induced to osteoblasts and adipocytes. The ITB group (dBMPC + nHAC/CSH) showed significantly more bone‐implant contact and bone density than either nHAC/CSH or control groups in the areas with peri‐implant defects 3 months after implantation.Conclusion: The results indicate that the ITB composed of nHAC/CSH and dBMPC may represent a useful strategy for the clinical reconstruction of bone defects around immediate implantation. However, further investigation is needed involving the use of human BMPC as well as possible use of stem cells.
Runaway accretion of metals from compact discs of debris on to white dwarfs
Authors: Rafikov Roman R. 
Published: July 2011

Abstract
It was recently proposed that metal-rich white dwarfs (WDs) accrete their metals from compact discs of debris found to exist around more than a dozen of them. At the same time, elemental abundances measured in atmospheres of some WDs imply vigorous metal accretion at rates up to 1011 g s−1, far in excess of what can be supplied solely by Poynting–Robertson drag acting on such discs of debris. To explain this observation we propose a model, in which rapid transport of metals from the disc on to the WD naturally results from interaction between this particulate disc and a spatially coexisting disc of metallic gas. The latter is fed by evaporation of debris particles at the sublimation radius located at several tens of WD radii. Because of pressure support the gaseous disc orbits the WD slower than the particulate disc. Resultant azimuthal drift between them at speed ≲1 m s−1 causes aerodynamic drag on the disc of solids and drives inward migration of its constituent particles. Upon reaching the sublimation radius, particles evaporate, enhancing the density of the metallic gaseous disc and leading to positive feedback. Under favourable circumstances (low viscosity in the disc of metallic gas and efficient aerodynamic coupling between the discs) a system evolves in a runaway fashion, destroying the discs of debris on time-scale of ∼105 yr, and giving rise to high metal accretion rates up to g s−1, in agreement with observations.
CARE/CEASA Roundtable on Managing Uncertainty and Risk
Authors: Harris Trevor , Shear Neal , Galbraith Steve 
Published: July 2011

Two distinguished Morgan Stanley “alumni” discuss how their management of risk and uncertainty has not only preserved but increased the profitability of their businesses. In both cases—one involving a commodities trading operation and the other a long‐short hedge fund—the key has been to find cost‐effective ways to “cut off the left tails” of the distribution by avoiding naked long or short positions and creating option‐like payoffs with limited downside.In the case of the hedge fund, the combination of longs and shorts with the use of other risk‐reducing strategies has enabled the fund's managers to produce twice the market's returns with only half the volatility (and only one losing year) during the 18‐year life of the fund. In the case of the commodities trading operation, the strategy is described as combining ownership of physical assets with the use of option pricing models to create what amount to “long gamma positions in the asset” that “produce payoffs regardless of whether the asset goes up or down in value.”
Accounting for Risk and Return in Equity Valuation
Authors: Penman Stephen 
Published: July 2011

Standard valuation models forecast cash flows or earnings, add a growth rate, and discount the cash flows to their present value with a discount rate that typically reflects the cost of capital. But as the author argues, projecting the long‐term growth rate is essentially speculative; and along with uncertainty about the growth rate, analysts generally do not have a good grasp of the discount rate either. Thus, instead of reducing uncertainty, these two features effectively compound uncertainty in valuations in the sense that slight changes in the growth rate or discount rate can change the valuation considerably.In this article, the author proposes an alternative approach that views the investor's problem as one of challenging the speculations that are built into the current market price, particularly the speculation about growth. Rather than building in a speculative growth rate (and thereby treating it as if it were a certainty), the author's approach turns the problem on its head by using an accounting analysis of the firm's current earnings and cash flows that provides a basis for recognizing the speculative component of the current stock price.More specifically, the author's analysis identifies the future earnings growth path that is implied by the market price, which can then be evaluated with the question: Do I want to pay for this growth? Because growth expectations are risky, additional analysis can be used to provide an understanding of the risk and return to buying growth, and of the upside and downside if risk growth expectations are not realized. By taking such an approach, investors incorporate their understanding of risk not by increasing the discount rate, but by recognizing that the primary risk in investing is the risk of overpaying for growth.