Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene therapy with adenovirus‐mediated VEGF enhances skin flap prefabrication

We investigated the feasibility in rats of enhancing skin‐flap prefabrication with subdermal injections of adenovirus‐encoding vascular endothelial growth factor (Ad‐VEGF). The left saphenous vascular pedicle was used as a source for vascular induction. A peninsular abdominal flap (8 × 8 cm) was elevated as distally based, keeping the epigastric vessels intact on both sides. After the vascular pedicle was tacked underneath the abdominal flap, 34 rats were randomly divided into three groups according to treatment protocol. The implantation site around the pedicle was injected with Ad‐VEGF in group I (n = 10), with adenovirus‐encoding green fluorescent protein (Ad‐GFP) in control group I (n = 14), and with saline in control group II (n = 10). All injections were given subdermally at four points around the implanted vessel by an individual blinded to the treatment protocol. The peninsular flap was sutured in its place, and 4 weeks later, an abdominal island flap based solely on the implanted vessels was elevated. The prefabricated island flap was sutured back, and flap viability was evaluated on day 7. Skin specimens were stained with hematoxylin and eosin for histological evaluation. In two rats from each group, microangiography was performed to visualize the vascularity of the prefabricated flaps. There was a significant increase in survival of prefabricated flaps in the Ad‐VEGF group compared to the control groups: Ad‐VEGF, 88.9 ± 6.1% vs. Ad‐GFP, 65.6 ± 9.4% (P<0.05) and saline, 56.0 ± 3.4% (P<0.05). Sections from four prefabricated flaps treated with Ad‐GFP revealed multiple sites of shiny deposits of green fluorescent protein around the area of local administration 1 day and 3 weeks after gene therapy. Histological examination done under high‐power magnification (×400) with a light microscope revealed increased vascularity and mild inflammation surrounding the implanted vessel in all groups. However, we were unable to demonstrate any significant quantitative difference with respect to vascularity and inflammatory infiltrates in prefabricated flaps treated with Ad‐VEGF compared with controls. Microangiographic studies showed increased vascularity around the implanted pedicle, which was similar in all groups. However, vascularization was distributed in a larger area in the prefabricated flaps treated with Ad‐VEGF. In this study, the authors demonstrated that adenovirus‐mediated VEGF gene therapy increased the survival of prefabricated flaps, suggesting that it may allow prefabrication of larger flaps and have the potential to reduce the time required for flap maturation. © 2005 Wiley‐Liss, Inc. Microsurgery 25:433–441, 2005.
Impact of Bromocriptine-QR Therapy on Glycemic Control and Daily Insulin Requirement in Type 2 Diabetes Mellitus Subjects Whose Dysglycemia Is Poorly Controlled on High-Dose Insulin: A Pilot Study

Background. The concurrent use of a postprandial insulin sensitizing agent, such as bromocriptine-QR, a quick release formulation of bromocriptine, a dopamine D2 receptor agonist, may offer a strategy to improve glycemic control and limit/reduce insulin requirement in type 2 diabetes (T2DM) patients on high-dose insulin. This open label pilot study evaluated this potential utility of bromocriptine-QR. Methods. Ten T2DM subjects on metformin (1-2 gm/day) and high-dose (TDID ≥ 65 U/day) basal-bolus insulin were enrolled to receive once daily (morning) bromocriptine-QR (1.6–4.8 mg/day) for 24 weeks. Subjects with at least one postbaseline HbA1c measurement (N = 8) were analyzed for change from baseline HbA1c, TDID, and postprandial glucose area under the curve of a four-hour mixed meal tolerance test (MMTT). Results. Compared to the baseline, average HbA1c decreased 1.76% (9.74 ± 0.56 to 7.98 ± 0.36, P = 0.01), average TDID decreased 27% (199 ± 33 to 147 ± 31, P = 0.009), and MMTT AUC60–240 decreased 32% (P = 0.04) over the treatment period. The decline in HbA1c and TDID was observed at 8 weeks and sustained over the remaining 16-week study duration. Conclusion. In this study, bromocriptine-QR therapy improved glycemic control and meal tolerance while reducing insulin requirement in T2DM subjects poorly controlled on high-dose insulin therapy.
A novel osteoclast precursor cell line, 4B12, recapitulates the features of primary osteoclast differentiation and function: Enhanced transfection efficiency before and after differentiation

Osteoclasts are bone‐resorbing multinucleated cells differentiated from monocyte/macrophage lineage precursors. A novel osteoclast precursor cell line, 4B12 was established from Mac‐1+c‐Fms+RANK+ cells from calvaria of 14‐day‐old mouse embryos using immunofluorescence and cell‐sorting methods. Like M‐CSF‐dependent bone marrow macrophages (M‐BMMs), M‐CSF is required for 4B12 cells to differentiate into TRAP‐positive multinucleated cells [TRAP(+) MNCs] in the presence of RANKL. Bone‐resorbing osteoclasts differentiated from 4B12 cells on dentine slices possess both a clear zone and ruffled borders and express osteoclast‐specific genes. Bone‐resorbing activity, but not TRAP, was enhanced in the presence of IL‐1α. The number of TRAP(+) MNCs and the number of pits formed from 4B12 cells on dentine slices was fourfold higher than that from M‐BMMs. 4B12 cells were identified as macrophages with Mac‐1 and F4/80, yet lost these markers upon differentiation into osteoclasts as determined by confocal laser scanning microscopy. The 4B12 cells do not have the potential to differentiate into dendritic cells indicating commitment to the osteoclast lineage. 4B12 cells are readily transfectable with siRNA transfection before and after differentiation. These data show that 4B12 cells faithfully replicate the properties of primary cells and are a useful and powerful model for analyzing the molecular and cellular regulatory mechanisms of osteoclastogenesis and osteoclast function. J. Cell. Physiol. 221: 40–53, 2009. © 2009 Wiley‐Liss, Inc
RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

Rosette nanotubes (RNT) are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif). In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C) and amino acid Lys (K-G∧C) which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS)-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 μg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1β, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.
Behavioral characterization of electric vehicle charging loads in a distribution power grid through modeling of battery chargers

Plug-in Electric Vehicle (PEV) is a new atypical load in power systems. In future, PEV load will play a significant role in the distribution grids. This integrated load into the power grid may overload the system components, increase power losses and may violate system constraints. Currently, the most common method of Electric Vehicle (EV) modeling is to consider the EV loads as constant power elements without considering the voltage dependency of EV charging system during state of charges (SOC). EV load demand cannot be considered as a constant power, as modeling as a constant power load will not provide accurate information about the behavior of charging system during charging process. As several research projects on smart grids are now looking into realistic models representing the realistic behavior of an EV loads, this paper proposes a methodology for modeling of EV charger integrated to an electricity grid in order to understand the impacts of EV charging load. A charging system was designed to capture the EV load behavior and extract the coefficients of the EV ZIP load model. A comparative study was carried out with different types of load models. The results indicate that the assumptions of load demand as a constant power to analysis the effect of PEVs on power grid would not be effective in real time application of PEVs.
Geoscience education and public outreach in Rocky Mountain National Park, Colorado, U.S.A.

&NA; Rocky Mountain National Park (RMNP) in north‐central Colorado exhibits a number of spectacular geologic features that exemplify geologic timescales and the breadth and power of geologic processes. Combined with the extensive system of trails, these features allow excellent access to effective Earth‐science educational opportunities. In July 2015, to help celebrate the centennial of RMNP, the author guided a geology‐based educational hike for the public on two occasions. The hiking route is approximately 15 km (˜9.3 mi) round‐trip and traverses through primarily Proterozoic metamorphic and igneous rocks that comprise the majority of bedrock in RMNP. In addition to crystalline bedrock, the route also incorporated observation of numerous glacial features and discussion of area hydrology and anthropogenic impacts. A post‐instructional survey indicates that the route and features observed helped to increase public awareness of geologic processes and sense of connection with the landscape. The route, although considered strenuous by the National Park Service, could be utilized for public outreach and geologic education for a wide variety of user groups.
Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling.

UNLABELLED Mesenchymal cells of the tumor-associated stroma are critical determinants of carcinoma cell behavior. We focus here on interactions of carcinoma cells with mesenchymal stem cells (MSC), which are recruited to the tumor stroma and, once present, are able to influence the phenotype of the carcinoma cells. We find that carcinoma cell-derived interleukin-1 (IL-1) induces prostaglandin E(2) (PGE(2)) secretion by MSCs. The resulting PGE(2) operates in an autocrine manner, cooperating with ongoing paracrine IL-1 signaling, to induce expression of a group of cytokines by the MSCs. The PGE(2) and cytokines then proceed to act in a paracrine fashion on the carcinoma cells to induce activation of β-catenin signaling and formation of cancer stem cells. These observations indicate that MSCs and derived cell types create a cancer stem cell niche to enable tumor progression via release of PGE(2) and cytokines. SIGNIFICANCE Although PGE2 has been implicated time and again in fostering tumorigenesis, its effects on carcinoma cells that contribute specifically to tumor formation are poorly understood. Here we show that tumor cells are able to elicit a strong induction of the COX-2/microsomal prostaglandin-E synthase-1 (mPGES-1)/PGE(2) axis in MSCs recruited to the tumor-associated stroma by releasing IL-1, which in turn elicits a mesenchymal/stem cell–like phenotype in the carcinoma cells.
Frontiers in Computational Neuroscience Computational Neuroscience

weak or absent elsewhere. Whether such a functionally clustered spatial organization of synaptic efficacy patterning may emerge as a result of synaptic plasticity is a question that is still being actively pursued. Notably, why would clustering be a desirable emergent prop-erty? Firstly, previous studies have illustrated non-linear summa-tion between nearby synchronous (or near-synchronous) synaptic inputs (Koch et al., 1983; Tuckwell, 1986; Polsky et al., 2004), allowing for easier spike generation in regions with clustered inputs. Other studies have shown that altering the spatial configuration of inputs changes firing properties (Mel, 1993; Poirazi et al., 2003; Iannella et al., 2004), while correlated activity can alter the integra-tive properties of neurons (Destexhe and Paré, 1999; Rudolph and Destexhe, 2003). Such clusters may provide part of the scaffolding underlying the emergence of functional dendritic compartments, subregions where activity tends to be correlated and where local signal integration permits some state-dependent non-linear computation to take place, but simultaneously different to what is happening in other compartments (Polsky et al. Importantly, various studies have indicated that plasticity may lead to arrange afferent fiber contacts into spatial clusters. Three-eyed frog experiments have shown that synapses contributed by
Endonasal Endoscopic Transsphenoidal Approach to Lesions of the Sellar Region in Pediatric Patients

Objective: Endoscopic endonasal (transnasal) transsphenoidal approach (EETA) for management of sellar lesions has gained popularity as a reliable and atraumatic method. Most reported studies of EETA have focused on surgical outcome in adult patients; and there are few reports to describe outcome in pediatric patients. The authors report our early experience of 11 patients aged 14 to 18 years managed with EETA to evaluate the safety and effectiveness of EETA in the pediatric. Methods: Retrospective review of hospital records of 11 pediatric patients who underwent endonasal endoscopic transsphenoidal approach for resection of sellar region lesion over 2 years. Age, sex, symptoms, tumor size, extent of tumor resection, clinical outcome, and surgical complications were reviewed. Results: Total resection was achieved in 9 (81.8%) patients, subtotal resection in 2 (18.2%), and no patient had partial or insufficient resection. All (100%) patients achieved visual remission, 7 (87.5%) of 8 patients with hyperhormone preoperative had endocrinological remission. Two (18.2%) patients incurred temporary diabetes insipidus (DI) postoperatively. One (9.1%) patient incurred postoperative cerebrospinal fluid (CSF) leakage which resolved following lumbar drainage. Three (27.3%) patients developed hypopituitarism needed hormone replacement therapy. There were no cases of meningitis, intracranial hematoma, or death. Conclusions: Endoscopic endonasal (transnasal) transsphenoidal approach (EETA) provides a safe and effective surgical option with low morbidity and mortality in pediatric patients.
Customizable coherent servo demodulation for disk drives

This paper describes the customizable coherent demodulation algorithm, a servo demodulator which provides dramatically improved performance over the currently used servo demodulation methods for disk drives. The demodulation algorithm proposed makes better use of knowledge about the read-back signal coming from the disk to provide better noise immunity and more immunity to other nonideal components in the magnetic head response. The net result is a demodulated position error signal which has a much cleaner response.
Post‐training cocaine exposure facilitates spatial memory consolidation in C57BL/6 mice

In this study, we examined the ability of post‐training injections of cocaine to facilitate spatial memory performance using the Morris water maze (MWM). We also investigated the role that hippocampal protein kinase A (PKA) and extracellular signal‐regulated kinase 1/2 (ERK) signaling may play in cocaine‐mediated spatial memory consolidation processes. Male and female C57BL/6 mice were first trained in a MWM task (eight consecutive trials) then injected with cocaine (0, 1.25, 2.5, 5, or 20 mg/kg), and memory for the platform location was retested after a 24 h delay. Cocaine had a dose‐dependent effect on spatial memory performance because only the mice receiving 2.5 mg/kg cocaine displayed a significant reduction in latency to locate the platform. No sex differences in MWM performance were observed; however, females showed higher hippocampal levels of PKA when compared with males. A second experiment demonstrated that 2.5 mg/kg cocaine enhanced MWM performance only when administered within 2, but not 4 h after spatial training. We also found that cocaine (2.5 mg/kg) increased ERK2 phosphorylation within the hippocampus and one of its downstream targets (ribosomal S6 kinase), a mechanism that may be responsible, at least in part, for the enhanced cocaine‐mediated spatial memory performance. Overall, these data demonstrate that a low dose of cocaine (2.5 mg/kg) administered within 2 h after training facilitates MWM spatial memory performance in C57BL/6 mice. © 2011 Wiley Periodicals, Inc.
Nitric Oxide-Mediated Antitumor Effects Migration of Immune Effector Cells and Stat3 Activity in Melanoma Cells Affects

Inﬁltration of immune effector cells in tumors is critical for antitumor immune responses. However, what regulates immune cell inﬁltration of tumors remains to be identiﬁed. Stat3 is constitutively activated with high frequency in diverse cancers, promoting tumor cell growth and survival. Blocking Stat3 signaling in tumors in vivo results in tumor growth inhibition that involves killing of nontransfected tumor cells and inﬁltration of immune effector cells, suggesting that Stat3 activity in tumor cells might affect immune cell recruitment. However, dying tumor cells can also attract immune cells. In this study, we show in isogenic murine melanomas that natural Stat3 activity is associated with tumor growth and reduction of T cell inﬁltration. Blocking Stat3 signaling in the melanoma cells containing high Stat3 activity results in expression of multiple chemoattractants, leading to increased migration of lymphocytes, NK cells, neutrophils, and macrophages. In addition, blocking Stat3 triggers tumor cells to produce soluble factors capable of activating macrophage production of NO in vitro and in vivo. TNF- (cid:1) and IFN- (cid:2) , which are secreted by Stat3-inhibited tumor cells, are able to activate macrophage NO production, whereas neutralizing TNF- (cid:1) in the tumor supernatant from Stat3-blocked tumor cells abrogates nitrite production. Moreover, interrupting Stat3 signaling in tumor cells leads to macrophage-mediated, nitrite-dependent cytostatic activity against nontransduced tumor cells. These results suggest that tumor Stat3 activity affects recruitment of diverse immune effectors and it can be manipulated to activate the effector phase of innate immune responses. The Journal of Immunology,
Renal failure in atherosclerotic renovascular disease: pathogenesis, diagnosis, and intervention

Atherosclerotic renovascular disease (ARVD) is increasingly recognised as an important cause of both chronic and end stage renal failure. These patients tend to do badly on dialysis, which reflects their systemic atherosclerotic burden. In an effort to delay and perhaps prevent their need for renal replacement therapy, some patients are subjected to a variety of medical, radiological and surgical interventions, although evidence for each is sparse. The purpose of this review is to describe the epidemiology and pathophysiology of renal failure in ARVD, discuss the available diagnostic techniques, consider the evidence for benefit from intervention in the context of pathogenesis and finally, identify those gaps in our knowledge which impede the practice of evidence based medicine. The prevalence of ARVD in patients with chronic renal failure is not known but dialysis registry data provide some epidemiological information about ARVD among patients who develop end stage renal failure (ESRF). Over a 20 year period in an American haemodialysis unit, Mailloux et al reported a 16% incidence of ARVD among new patients with a median age of 70 years (range 37–86 years). 1 Similarly, in an 18 month retrospective study in a UK haemodialysis unit, Scoble et al reported a 14% incidence of ARVD among patients over the age of 50 years.2 ESRF patients with ARVD generally present with substantial comorbidities and have a poor prognosis on dialysis.1 Given their poor prospects, many patients may not be offered dialysis and therefore these figures are likely to underestimate the true incidence of the disease. These studies do identify age as a risk factor for ARVD and a cause for ESRF. Consistent with this, in a series of 133 hypertensive patients with chronic renal failure (mean (SD) creatinine clearance 51(26) ml/min) not due to glomerulonephritis or polycystic kidney disease, the incidence of …
Evaluating Outcomes of Alternative Dosing Strategies for Cefepime

Objective: To perform a qualitative systematic review of the evidence comparing traditional with prolonged intermittent or continuous infusions of cefepime based on clinical and pharmacodynamic outcomes. Data Sources: PubMed (1946 to October 2014), EMBASE (1980 to October 2014), CENTRAL, Cochrane Database of Systematic Reviews, Web of Science, and International Pharmaceutical Abstracts (1970 to October 2014) were searched using the terms cefepime, pharmacokinetics, pharmacodynamics, drug administration, intravenous infusions, intravenous drug administration, continuous infusion, extended infusion, and intermittent therapy. Reference lists from relevant materials were reviewed. Study Selection and Data Extraction: Articles evaluating administration regimens of cefepime, one of which included the traditional, manufacturer-recommended 0.5-hour infusion and the other a prolonged or continuous infusion were included. Prespecified clinical outcomes of interest included all-cause mortality, length of hospital stay, clinical cure, and adverse events. The primary pharmacodynamic outcome was percentage time of unbound drug concentration remaining above the minimum inhibitory concentration. Data Synthesis: In all, 18 studies were included; 6 studies assessed clinical outcomes, and 12 assessed pharmacodynamic outcomes. Prolonged or continuous infusions of cefepime achieved the pharmacodynamic targets more often than traditional infusions. The association of improved clinical outcomes with prolonged or continuous infusions is unclear. All-cause mortality was significantly decreased with the use of a prolonged cefepime infusion in a retrospective study. Two prospective, randomized studies demonstrated no statistically significant difference in mortality between prolonged and intermittent infusions. Conclusions: The available literature on prolonged and continuous infusions of cefepime demonstrated an improved achievement of pharmacodynamic targets; however, the effect on clinical outcomes is inconclusive. Well-designed prospective studies are required to determine optimal dosing and administration strategies.