Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of triazolopyrimidine on lipid peroxidation and nitric oxide levels in the corticosteroid‐impaired healing of rat tracheal anastomoses

Corticosteroids are used to reduce the oedema and prevent scar tissue formation of the upper airways by their ability to inhibit influx of inflammatory cells, limit capillary permeability and block collagen synthesis in the early stages of wound healing. Triazolopyrimidine (Trapidil) is an antiplatelet agent that acts in part as a phosphodiesterase inhibitor and as a competitive inhibitor of the platelet‐derived growth factor (PDGF) receptor. Trapidil, with its vasodilator and NO releasing effect may have some potential to diminish the tissue injury. This study was carried out to evaluate the effects of trapidil (triazolopyrimidine) on lipid peroxidation and nitric oxide in the corticosteroid‐impaired healing of tracheal anastomoses. Thirty‐four adult Wistar rats were divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: group I, control, (GI, n = 6); group II, sham, (GII, n = 6); group III, dexamethasone, 0.1 mg kg−1 twice daily intramuscularly, (GIII, n = 8); group IV, trapidil, 6 mg kg−1 twice daily intraperitoneally (GIV, n = 7); group V, dexamethasone, 0.1 mg kg−1 plus trapidil, 6 mg kg−1 twice daily (GV, n = 7), for 1 week. After 1 week, anastomotic healing was assessed by measurement of bursting pressure, evaluation of histopathology, measurement of MDA and nitrite/nitrate levels. In GIII, GIV and GV bursting pressures resulted in significantly reduced anastomotic strength compared to the controls (p < 0.001 for all groups). The difference between bursting pressures of GIII and GIV was not found to be statistically significant (p = 0.966). In regard to fibroblast proliferation and collagen content, a significant difference was found between GIII and GI (p < 0.01), A significant difference was also found when GIV and GV were compared to GIII (p < 0.01). MDA and nitrite/nitrate levels were found to be higher in GIII when compared to all other groups. MDA levels of GIV and GV rats were found to be lower than GIII (p < 0.001, for both groups). The nitrite/nitrate levels of GIV and GV rats were found to be lower than GIII (p < 0.05), and higher than GI (p < 0.001). Trapidil may be useful for its preventive effects on lipid peroxidation and possible increases in NO in cases with corticosteroid‐impaired healing of trachea anastomoses. Copyright © 2004 John Wiley & Sons, Ltd.
Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of αvβ3 Integrin Expression with Gallium-68

Tris(hydroxypyridinone) chelators conjugated to peptides can rapidly complex the positron-emitting isotope gallium-68 (68Ga) under mild conditions, and the resulting radiotracers can delineate peptide receptor expression at sites of diseased tissue in vivo. We have synthesized a dendritic bifunctional chelator containing nine 1,6-dimethyl-3-hydroxypyridin-4-one groups (SCN-HP9) that can coordinate up to three Ga3+ ions. This derivative has been conjugated to a trimeric peptide (RGD3) containing three peptide groups that target the αvβ3 integrin receptor. The resulting dendritic compound, HP9-RGD3, can be radiolabeled in 97% radiochemical yield at a 3-fold higher specific activity than its homologues HP3-RGD and HP3-RGD3 that contain only a single metal binding site. PET scanning and biodistribution studies show that [68Ga(HP9-RGD3)] demonstrates higher receptor-mediated tumor uptake in animals bearing U87MG tumors that overexpress αvβ3 integrin than [68Ga(HP3-RGD)] and [68Ga(HP3-RGD3)]. However, concomitant nontarget organ retention of [68Ga(HP9-RGD3)] results in low tumor to nontarget organ contrast in PET images. On the other hand, the trimeric peptide homologue containing a single tris(hydroxypyridinone) chelator, [68Ga(HP3-RGD3)], clears nontarget organs and exhibits receptor-mediated uptake in mice bearing tumors and in mice with induced rheumatoid arthritis. PET imaging with [68Ga(HP3-RGD3)] enables clear delineation of αvβ3 integrin receptor expression in vivo.
Prehospital advanced airway management by ambulance technicians and paramedics: is clinical practice sufficient to maintain skills?

Introduction: Ambulance paramedics are now trained routinely in advanced airway skills, including tracheal intubation. Initial training in this skill requires the insertion of 25 tracheal tubes, and further ongoing training is attained through clinical practice and manikin-based practice. In contrast, training standards for hospital-based practitioners are considerably greater, requiring approximately 200 tracheal intubations before practice is unsupervised. With debate growing regarding the efficacy of paramedic intubation, there is a need to assess current paramedic airway practice in order to review whether initial training and maintenance of skills provide an acceptable level of competence with which to practice advanced airway skills. Methods: All ambulance patient report forms (anonymised) for the period 1 January 2007 to 31 December 2007 were reviewed, and data relating to airway management were collected. Paramedic and technician identification codes were used to determine the number of airway procedures undertaken on an individual basis. Results: Of the 269 paramedics, 128 (47.6%) had undertaken no intubation and 204 (75.8%) had undertaken one or less intubation in the 12-month study period. The median number of intubations per paramedic during the 12-month period was 1.0 (range 0–11). A total of 76 laryngeal mask insertion attempts were recorded by 41 technicians and 30 paramedics. The median number of laryngeal mask insertions per paramedic/technician during the 12-month period was 0 (range 0–2). A survey of ongoing continuing professional development across all ambulance trusts demonstrated no provision for adequate training to compensate for the lack of clinical exposure to advanced airway skills. Conclusion: Paramedics use advanced airway skills infrequently. Continuing professional development programmes within ambulance trusts do not provide the necessary additional practice to maintain tracheal intubation skills at an acceptable level. Advanced airway management delivered by ambulance crews is likely to be inadequate with such infrequent exposure to the skill.
Striving for Product Development Excellence - Lessons Learned from the Implementation of Lean Management

This chapter builds upon and extends the discussion about knowledge creation processes in New Product Development (NPD). We refine Nonaka’s (1994) SECI model by focusing on what and – more specifically – who triggers the transition across the different knowledge creation modes, i.e. socialization, externalization, combination and internalization. To do so, this study integrates Nonaka’s distinction between different forms of knowledge – tacit vs. explicit – with Davenport’s (1993) distinction in terms of knowledge content – process knowledge (the knowledge of how to develop products) vs. improvement knowledge (the knowledge of how to improve business processes). This chapter delivers a threefold contribution to the literature on organizational learning. First, we show that the starting point of Nonaka’s learning spiral varies with the knowledge content. Second, we argue that the learning spirals of process knowledge and improvement knowledge are connected. Finally, we will show that this link is established by specific organizational roles, which we call continuous improvement facilitators, who match, in a garbage can logic, the solutions embedded in the improvement knowledge to the problems identified through process knowledge.
Human Resource Strategies for International Growth

1. Internationalization and the Domestic Firm 2. Going International 3. The Role of Alliances in Internationalization 4. Human Resource Management in the International Firm 5. Internationalization and the Single European Market 6. The Single European Market and the HRM Response 7. Concluding Comments - HRM and the 1990s.
What are the barriers to investing in social enterprises? An investigation into the attitudes and experiences of social entrepreneurs in the United Kingdom

The ongoing global economic crisis and the restrictions that this is having on government expenditure has meant that current UK policy is being directed at trying to end the grant dependency that currently exists in the third sector. One of the key focuses of this policy initiative has been to try to increase the third sector’s access to both debt finance from lending institutions and equity finance from venture capital investors. However, this policy intervention presupposes that the lack of private sector investment in the third sector is a ‘supply-side’ problem caused by limited funds. This ignores the structural problems in the social enterprise sector related to governance and a lack of organisational capacity. Indeed, as of 2011 the ethical investment sector in the UK was worth approximately £9 billion and was spread across 90 ethical investment funds responsible to 700,000 investors. Additionally, social investment (i.e. those funds targeted specifically at third sector organisations) was worth £165 million as of 2011. This suggests that the lack of private sector investment in social enterprises in the UK is not a ‘supply’ side problem but is instead related to the ‘investment readiness’ of social enterprises
Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation

The effect of meningococcal cell-associated sialic acid on activation of the human alternative complement pathway was examined by using a quantitative fluorescence immunoassay to assess alternative pathway-mediated C3 binding to a group B strain of Neisseria meningitidis from which graded amounts of sialic acid had been removed with neuraminidase. Using human serum absorbed with strain B16B6 (B:2a:L2,3) and chelated with 10 mM MgCl2 and 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, we found an increase in the amount of C3 bound by enzymatically desialylated B16B6 organisms over the amount bound by fully sialylated organisms. This increase was proportional to the amount of sialic acid cleaved from the bacteria. Enhanced C3 binding was accompanied by an increase in factor B deposition. A sialic acid-deficient mutant of strain B16B6, designated 2T4-1, bound C3 via the alternative pathway at a level equivalent to that bound by wild-type meningococci from which 88% of the sialic acid had been removed. Strain B16B6 was resistant to the alternative pathway-mediated bactericidal activity of both absorbed and hypogammaglobulinemic human sera, whereas noncapsular variant 2T4-1 was sensitive to these sera. The addition of purified immune immunoglobulin M (IgM) and IgG significantly increased the alternative pathway-mediated killing of strain B16B6 organisms. IgM mediated increased bactericidal activity without an increase in C3 or factor B deposition. In contrast, the IgG-mediated killing was associated with increased binding of C3 and factor B to the organisms. Absorption studies showed that the IgM bound to the sialic acid capsule, whereas the IgG bound to noncapsular surface antigens. We conclude from these results that the group B meningococcal sialic acid capsule inhibits activation of the alternative pathway in the nonimmune host and that both IgM and IgG, although specific for different surface antigens, are capable of augmenting the alternative pathway-mediated killing of group B meningococci.
Transient serum exposure regimes to support dual differentiation of human mesenchymal stem cells

Human mesenchymal stem cells (MSCs), which can generate both osteoblasts and chondrocytes, represent an ideal resource for orthopaedic repair using tissue‐engineering approaches. One major difficulty for the development of osteochondral constructs using undifferentiated MSCs is that serum is typically used in culture protocols to promote differentiation of the osteogenic component, whereas existing chondrogenic differentiation protocols rely on the use of serum‐free conditions. In order to define conditions which could be compatible with both chondrogenic and osteogenic differentiation in a single bioreactor, we have analysed the efficiency of new biphasic differentiation regimes based on transient serum exposure followed by serum‐free treatment. MSC differentiation was assessed either in serum‐free medium or with a range of transient exposure to serum, and compared to continuous serum‐containing treatment. Although osteogenic differentation was not supported in the complete absence of serum, marker expression and extensive mineralization analyses established that 5 days of transient exposure triggered a level of differentiation comparable to that observed when serum was present throughout. This initial phase of serum exposure was further shown to support the successful chondrogenic differentiation of MSCs, comparable to controls maintained in serum‐free conditions throughout. This study indicates that a culture based on temporal serum exposure followed by serum‐free treatment is compatible with both osteogenic and chondrogenic differentiation of MSCs. These results will allow the development of novel strategies for osteochondral tissue engineering approaches using MSCs for regenerative medicine. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of the Mechanism and Magnitude of Cytoglobin-mediated Nitrite Reduction and Nitric Oxide Generation under Anaerobic Conditions*

Background: Cytoglobin plays cytoprotective roles under hypoxic/ischemic conditions, but the mechanisms remain unclear. Results: Cytoglobin functions as a nitrite reductase leading to NO generation and soluble guanylyl cyclase activation under anaerobic or severely hypoxic conditions and this is increased by acidosis as occurs in ischemia. Conclusion: Cytoglobin-mediated nitrite reduction generates NO that activates soluble guanylyl cyclase under hypoxic/ischemic conditions. Significance: Cytoglobin serves a protective function by reducing nitrite to NO under ischemic conditions. Cytoglobin (Cygb) is a recently discovered cytoplasmic heme-binding globin. Although multiple hemeproteins have been reported to function as nitrite reductases in mammalian cells, it is unknown whether Cygb can also reduce nitrite to nitric oxide (NO). The mechanism, magnitude, and quantitative importance of Cygb-mediated nitrite reduction in tissues have not been reported. To investigate this pathway and its quantitative importance, EPR spectroscopy, spectrophotometric measurements, and chemiluminescence NO analyzer studies were performed. Under anaerobic conditions, mixing nitrite with ferrous-Cygb triggered NO formation that was trapped and detected using EPR spin trapping. Spectrophotometric studies revealed that nitrite binding to ferrous-Cygb is followed by formation of ferric-Cygb and NO. The kinetics and magnitude of Cygb-mediated NO formation were characterized. It was observed that Cygb-mediated NO generation increased linearly with the increase of nitrite concentration under anaerobic conditions. This Cygb-mediated NO production greatly increased with acidosis and near-anoxia as occur in ischemic conditions. With the addition of nitrite, soluble guanylyl cyclase activation was significantly higher in normal smooth muscle cells compared with Cygb knocked down cells with Cygb accounting for ∼40% of the activation in control cells and ∼60% in cells subjected to hypoxia for 48 h. Overall, these studies show that Cygb-mediated nitrite reduction can play an important role in NO generation and soluble guanylyl cyclase activation under hypoxic conditions, with this process regulated by pH, oxygen tension, nitrite concentration, and the redox state of the cells.
Twin Pregnancy: Complications and Treatment

Early identification of the high-risk twin pregnancy makes preventive intervention possible. Bed rest is commonly used to improve the outcome of twin pregnancies, but its value is not clearly established. A physiologic and clinical search for meaningful interventions is in order, for reduction of twin morbidity and mortality would significantly alter the overall perinatal morbidity and mortality rates.
Inventory and Shipment Policies for the Online Movie DVD Rental Industry

The online movie rental industry in the United States has grown at a rapid pace during the past decade. Netflix and Blockbuster are two prime examples of companies that operate in this arena, each with a large subscriber base. These two companies employ two standard methods for movie delivery: streaming and DVD-by-mail services. Although the industry is clearly undergoing a transition into streaming service, a substantial fraction of subscribers continue to prefer the more traditional DVD-by-mail service. We will study the problem of how to efficiently manage DVD-by-mail service. An essential task in solving our problem is a proper modeling of subscriber demand. We will therefore first develop a demand formulation based on data from Blockbuster. This formulation is then used to construct a nonlinear mathematical program for making the following decisions: i the initial order quantity of a new movie DVD title and ii the shipment size of the title for every period i.e., day after its release. By exploiting the structure of this mathematical program, we develop a heuristic algorithm based on a simple shipment policy. Through extensive computational experiments, we demonstrate that our algorithm provides optimal or close to optimal solutions for practically relevant problem instances. The proposed policy and solution are simple, easy to understand, and easily implementable in practice.
Factors associated with iohexol-based glomerular filtration rate slope over 36 months in HIV-negative and HIV-positive individuals

Background:Monitoring kidney function is important in HIV-positive persons, but creatinine-based estimates of glomerular filtration rate (GFR) have limitations. There are little to no data available assessing GFR trends in HIV-positive persons using a gold-standard measure of GFR. Methods:We measured GFR based on iohexol plasma disappearance (iGFR) annually for 3 years in nondiabetic, HIV-negative and HIV-positive volunteers with normal estimated kidney function. We used mixed linear models to evaluate factors associated with baseline iGFR and iGFR slope. Results:One hundred HIV-negative and 191 HIV-positive, predominantly black individuals (median age 49 years) participated in the study and completed a total of 960 iGFR assessments over a median of 36 months. Despite similar estimated GFR at baseline, average iGFR values were lower in HIV-positive compared with HIV-negative participants (103.2 vs. 110.8, ml/min/1.73 m2, P = 0.004). However, subsequent iGFR slope was not significantly different in HIV-positive and HIV-negative participants. In the HIV-positive group, the presence of carotid plaque and hepatitis C virus coinfection were associated with significantly lower iGFR values at baseline. A nonsuppressed HIV RNA level at baseline was associated with a significantly more rapid iGFR decline compared with individuals with HIV RNA less than 400 copies/ml (−4.69 vs. −1.31 ml/min per 1.73 m2 per year, P = 0.005). Other factors significantly associated with iGFR slope included albuminuria and glycosylated hemoglobin. Conclusion:Compared with HIV-negative persons, HIV-positive participants had significantly lower baseline iGFR, despite similar estimated GFR in the two groups. Nonsuppressed HIV RNA at baseline was associated with a more rapid iGFR decline over 3 years.
Strain-induced optical changes in demineralized bone

Abstract. Bone “stress-whitens,” becoming visibly white during mechanical loading, immediately prior to failure. Stress-whitening is known to make materials tougher by dissipating mechanical energy. A greater understanding of stress-whitening, both an optical and mechanical phenomenon, may help explain age-related increases in fracture risk that occur without changes in bone mineralization. In this work, we directly measure the optical properties of demineralized bone as a function of deformation and immersing fluid (with different hydrogen-bonding potentials, water, and ethanol). The change in refractive index of demineralized bone was linear: with deformation and not applied force. Changes in refractive index were likely due to pushing low-refractive-index fluid out of specimens and secondarily due to changes in the refractive index of the collagenous phase. Results were consistent with stress-whitening of demineralized bone previously observed. In ethanol, the refractive index values were lower and less sensitive to deformation compared with deionized water, corroborating the sensitivity to fluid hydration. Differences in refractive index were consistent with structural changes in the collagenous phase such as densification that may also occur under mechanical loading. Understanding bone quality, particularly stress-whitening investigated here, may lead to new therapeutic targets and noninvasive methods to assess bone quality.
Transducing phages for Bacillus subtilis.

SUMMARY Transducing phage PBS1 and a clear-plaque type mutant PBS2 derived from PBS1 show similar growth characteristics with a relatively small burst size (23 to 24), and are related serologically. They are morphologically indistinguishable and both have a dense head of about 100 mμ in diameter and a tail about 250 mμ in length. PBS 1 is more efficient in trans-duction and its plaque-forming activity is more sensitive to ultraviolet (u.v.) irradiation than that of PBS2. The host range of the phages is limited to strains of Bacillus subtilis. All Marburg strains tested were sensitive to the lytic action of the phages. Prophages of PBS1 and PBS 2 were not u.v. -inducible and the irradiation of lysogenic cultures with a relatively high dose of u.v. radiation resulted in considerable decrease of the free phage titre. However, transducing activities of lysates treated with a high dose of u.v. radiation were not affected significantly. Organisms lysogenic either for PBS 1 or to PBS 2 were not stable and reverted to the sensitive state.
Role of Erbb2 in Selection for Adjuvant Tamoxifen or Aromatase Inhibitors

Evaluation of: Rasmussen BB, Regan MM, Lykkesfeldt AE et al.: Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1–98 randomized trial. Lancet Oncol. 9, 23–28 (2008). This study analysed data after a median of 51 months follow-up from 4922 postmenopausal women with early hormone-sensitive breast cancer randomly assigned to 5 years of treatment with letrozole or tamoxifen. Tumors from 3650 (74%) patients were centrally assessed for estrogen receptor, progesterone receptor and ErbB2 status. By central assessment, 7% (257 of 3650) of tumors were classified as ErbB2-positive. Disease-free survival was significantly worse in patients with ErbB2-positive tumors (p < 0.0001). Letrozole improved disease-free survival compared with tamoxifen regardless of ErbB2 status.