High Target Research Articles

Randomized Controlled Trial of Oxygen Saturation Targets in Very Preterm Infants: Two Year Outcomes

To assess whether an oxygen saturation (Spo2) target of 85%-89% compared with 91%-95% reduced the incidence of the composite outcome of death or major disability at 2 years of age in infants born at <28 weeks' gestation. A total 340 infants were randomized to a lower or higher target from <24 hours of age until 36 weeks' gestational age. Blinding was achieved by targeting a displayed Spo2 of 88%-92% using a saturation monitor offset by ±3% within the range 85%-95%. True saturations were displayed outside this range. Follow-up at 2 years' corrected age was by pediatric examination and formal neurodevelopmental assessment. Major disability was gross motor disability, cognitive or language delay, severe hearing loss, or blindness. The primary outcome was known for 335 infants with 33 using surrogate language information. Targeting a lower compared with a higher Spo2 target range had no significant effect on the rate of death or major disability at 2 years' corrected age (65/167 [38.9%] vs 76/168 [45.2%]; relative risk 1.15, 95% CI 0.90-1.47) or any secondary outcomes. Death occurred in 25 (14.7%) and 27 (15.9%) of those randomized to the lower and higher target, respectively, and blindness in 0% and 0.7%. Although there was no benefit or harm from targeting a lower compared with a higher saturation in this trial, further information will become available from the prospectively planned meta-analysis of this and 4 other trials comprising a total of nearly 5000 infants.

Abstract 68: Safety and Effectiveness of Intensive Blood Pressure Management in the Elderly: Findings From the Secondary Prevention of Small Subcortical Strokes Trial

Background: Despite being at greatest risk for stroke, older adults are less likely to receive the same level of vascular risk factor management as younger adults. Our objective was to examine the safety and effectiveness of intensive systolic blood pressure (SBP) management in the elderly cohort of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. Methods: SPS3 is an international trial that evaluated SBP targets (&lt; 130 mmHg vs. 130-149 mmHg) for secondary stroke prevention in patients with recent lacunar stroke. Elderly were defined as ≥ 75 years at study entry and compared with patients &lt; 75 years on adherence to SBP targets, presence of side-effects, and risk of recurrent stroke, cardiac events, and death. Interactions between age and SBP targets on outcomes were examined. Results: Of the 3020 participants in SPS3, 494 (16%) were ≥ 75 years (mean age 80 years). Mean achieved SBP across all follow-ups was similar (older and younger groups respectively, lower target: 125.2 (15.8) vs. 125.1 (14.4), p=0.62; higher target: 137.1 (14.6) vs. 137.1 (14.4), p=0.95). Adherence to medications and follow-up visits was similar. There was no difference by age group in rates of postural hypotension and serious complications of hypotension. There was no difference in the effect of the SBP intervention by age group on stroke (p=0.39), cardiac events (p=0.62), and all-cause mortality (p=0.29). There was a significant interaction for vascular death (p=0.049). While there was no association with SBP treatment group and vascular death in the younger group (HR: 1.17; 95% CI: 0.68-2.01), there was a significant reduction in vascular death for the elderly in those assigned to the lower target (HR: 0.42; 95% CI: 0.18-0.98). Conclusions: These results provide evidence that elderly (≥75 years) can safely tolerate lowering of SBP. In addition to similar benefit as their younger counterparts regarding stroke, cardiac events, and all cause mortality, elderly SPS3 participants had a decreased risk of vascular death. To decrease the growing stroke burden it is critical that age disparities in treatment are eliminated.

Similar Outcomes for Two Anemia Treatment Strategies among Elderly Hemodialysis Patients with Diabetes.

To compare mortality and cardiovascular risk in elderly dialysis patients with diabetes under two clinical strategies of anemia correction: maintaining hematocrit (Hct) between 34.5 and < 39.0% (high Hct strategy), and between 30.0 and <34.5% (low Hct strategy) using intravenous alpha epoetin. Observational data were used to emulate a randomized trial in which diabetic patients who initiated hemodialysis in 2006-2008 were assigned to each anemia correction strategy. Inverse-probability weighting was used to adjust for measured time-dependent confounding. Comparing high with low hematocrit strategy, the hazard ratio (95% confidence interval) was 1.07 (0.83, 1.38) for all-cause mortality and 1.00 (0.81, 1.24) for a composite mortality and cardiovascular endpoint. Among a cohort of elderly hemodialysis patients with diabetes, no differences were found between the low and high hematocrit strategies. A lower target hematocrit - per current Food and Drug Administration (FDA) guidelines - appears to be as safe as higher targets among this population.

Enhanced discharge of high power pulsed magnetron sputtering coupling with high voltage

Plasma source ion implantation and deposition, as an effective technology to produce functional coatings with high adhesion and density, possesses the wide application prospect, especially in the deposition of coatings that work in high loading service conditions. The key component of this technology is the metal plasma source, which is now based on pulsed cathodic arc with complex source structure and magnetic filtration because of the macro-droplets in the ion flux. In this paper, we present another metal plasma source, high power pulsed magnetron sputtering (HPPMS), and investigate the discharge characteristics at different coupling high-voltages by optical emission spectroscopy. The results show that significant improvements are found in the discharge target current and main particles in the plasma. The improvement in gas discharge by the coupling high-voltage is greater than in metal discharge which could increase obviously in the self-sputtering stage with higher target voltage discharge. Last but not least, in this paper we discuss the discharge enhancing mechanism of coupling high-voltage. It is found that the self-excited glow discharge of coupling high-voltage, the hollow-cathodic effect induced by face-to-face negative voltages of HPPMS and coupling high-voltage, and the enhanced ambipolar diffusion of the coupling high-voltage can all play a considerable role in HPPMS discharge.

When should venture capitalists exit their investee companies?

Purpose – Exit strategies are critical for external private equity holders, such as venture capitalists and business angels, to receive investment returns successfully. The paper models the exit decision as a fixed date with the option to exit early, and develop an approach to help private equity holders determine an optimal early exit region based on a target equity value and the time remaining. Design/methodology/approach – The paper sets up a continuous time model to derive analytical solutions and apply simulations to numerical examples in this study. Findings – By numerically analyzing the nature of the solution the paper illustrates that a higher return drift of the investee company, a lower return volatility of the investee company, and a higher target return of the private equity holder results a smaller early exit region. Originality/value – This study helps determine the optimal time of stopping investments, and provides venture capitalists with a usable way to make exit decisions.

Single-stent crossover technique from distal unprotected left main coronary artery to the left circumflex artery

Objectives: To report the clinical outcomes of single-stenting from distal unprotected left main coronary artery (LMCA) to the left circumflex artery (LCx). Background: Percutaneous coronary intervention of distal LMCA is usually performed by stenting into the left anterior descending artery (LAD). In some cases, stenting from LMCA to LCx alone is performed. Methods: Between April 2002 and April 2011, single-stenting with drug-eluting stent for distal unprotected LMCA disease was performed in 584 patients. Thirty-one patients underwent LMCA-LCx stenting, who were compared with the remaining 553 LMCA-LAD stented patients. Results: At 3-year follow-up, there were no significant differences between LMCA-LCx and LMCA-LAD stenting groups in major adverse cardiac events (24.1% vs. 19.6%, p=0.540), cardiac death and myocardial infarction. A trend towards higher target lesion revascularization (TLR) in the LMCA-LCx stenting group was noted. This was significant when the stented-branch was only considered (18.2% vs. 3.0%, p<0.001). In both TLR-subgroups, LCx-ostium was frequently involved (83.3% in LMCA-LCx vs. 66.2% in LMCA-LAD TLR-subgroups, p=0.39). The LAD-ostium was more frequently involved in LMCA-LCx TLR-subgroup (83.3% vs. 21.0%, p<0.001). On the multivariable Cox regression analysis, LMCA-LCx stenting was an independent predictor of TLR for restenosis at the ostium of the stented-branch (HR 6.49, 95% CI 2.27-18.53, p<0.001). Conclusions: TLR rate at the LCx-ostium is high irrespective of LMCA-LCx or LMCA-LAD stenting. The former also seems to be associated with high TLR at the LAD-ostium. It may therefore be important to evaluate alternative strategies for treating distal LMCA disease that extends into the LCx but not LAD.

Comparison between long versus short chronic total occlusion intervention with drug-eluting stents; Six-month angiographic and 2-years clinical outcomes

Background: Chronic Total Occlusion (CTO) intervention is still challenging because of the limited procedural success rate and higher target failure. It is not clear whether the angiographic and clinical outcomes of diffuse long CTO can be different with those of short CTO in the drug eluting stent (DES) era. Methods: A total of 235 consecutive patients (pts) underwent CTO intervention were divided into two groups according the CTO lesion length (Diffuse long group,≥30mm: n=159 pts, Control group, <30mm: n=76 pts). Six-month angiographic and 24-month clinical outcomes were compared between the two groups. Results: The baseline clinical characteristics were similar between the two groups except prior PTCA was more frequent in diffuse long CTO group whereas bifurcation lesion was more frequent in the control group. In-hospital complications were similar between the two groups except intimal dissection was more frequent in diffuse long CTO group. Both groups had similar angiographic outcomes at 6 months and clinical outcomes up to 2 years except repeat PCI, predominantly target vessel revascularization (TVR) was higher in the diffuse long CTO group (Table). In multivariate analysis, diffuse long CTO was a important predictor for repeat PCI (OR; 4.269, CI 1.53-11.9, p=0.006). ![Figure][1] Conclusion: The safety profile, long-term angiographic and clinical outcomes were similar between the two groups except higher repeat PCI in the diffuse long CTO group despite of DES implantation. Long-term randomized clinical trials with larger study population will be necessary to elucidate the final conclusion. [1]: pending:yes

Advanced indium tin oxide ceramic sputtering targets (rotary and planar) for transparent conductive nanosized films

Indium tin oxide (ITO) ceramic sputtering targets used for the manufacturing of transparent conductive thin films for electrodes in flat panel displays, solar cells, touch panels, antistatic films and others developed and commercially produced are described. Thanks to optimised compositions and developed technology, commercially producing large size planar and new generation rotary ceramic target components have high density (up to 99·5% of theoretical density), uniform microcrystalline structure and superior properties, e.g. low electrical resistivity. As a result, nanosized thin films produced by direct current magnetron sputtering from the developed targets have uniform nanocrystalline or amorphous structures and superior transmittance (>90%) and low electrical resistivity. The morphology and properties of these films have been studied, depending on the film processing features. The benefits of the developed ITO rotary targets for industrial nanosized film processing (e.g. significant increase in process efficiency, about three times higher target utilisation, practically no nodule formation and particle redeposition during sputtering and reduced processing cost) are outlined.

Reevaluating FMOLP Decision Variable Coefficients Using the SWAT Results for the Optimization of Sustainable Agricultural Land Use in Small Watershed

The inappropriate use of agricultural land has caused several environmental and socio-economic problems. Fuzzy multiple objectives linear programming (FMOLP) is a mathematical technique that can be effective in land use planning. It requires decision variable coefficients (DVCs) to formulate the problem model covering all environmental and socio-economic aspects. The solution from a formulated FMOLP model provides optimal land use proportion and then the proportion is relocated t o produce the land use planning map. The map is then transferred to the soil and water assessment tools (SWAT) for assessing the impacts. The SWAT results give out a value which differs from the initial DVCs in the comparable aspects. This difference indicates that the initial DVCs were not realistic for the selected watershed and the land use planning map were not optimal. This study attempts to reevaluate DVCs in the FMOLP model by designing a method of sustainable agricultural land-use planning which makes use of the outputted results from the SWAT model. The results in terms of soil loss, crop water consumption, crop yields and net profit are simulated by SWAT and then replace to the DVC’s value. This procedure will be repeated until a small difference between SWAT results and DVC’s values are obtained. The findings of this study show that the final land use map achieves a higher target value than the map that was constructed after the initial phase of testing in all of objective. It is hoped the outcomes of this loop back process can be linked to the optimizing technique, so that environmental models can be utilized in the model output to improve optimum proportional solutions in any decision support system (DSS) for future sustainable agricultural land use planning.

TH-A-137-09: Gated Lung SRS/SBRT with Conical Collimators

Purpose: To investigate the use of conical collimator equipped linacs to treat small lung tumors (< 3 cm in diameter) with gated stereotactic radio-surgery (SRS) or stereotactic body radio-therapy (SBRT) and to compare the performance of this modality with other treatment options currently being used. Methods: A phantom simulating chest and lung motion was used to test the effectiveness of gating a linac equipped with conical collimators. Dose to a simulated lung lesion was planned, delivered using cones, and measured with an ionization chamber and film. Plans designed using traditional modalities for treatment of a single, small lung lesion were then compared with plans using conical collimators to determine if any advantages exist when using conical collimators. Results: Conical collimator equipped linacs may be used with respiratory gating during SRS/SBRT. For Varian Trilogy linacs, using beam arcs with cones rather than static beams would require software modifications that prevent minor-interlocks from reinitiating the beam after gantry motion is stopped due to gating. A significant advantage was found when using static beams with cylindrical collimators to treat small lung lesions where the healthy tissue at risk is limited by mean dose to the tissue. It is possible to deliver 30% higher doses to the target lesion under these circumstances. When the healthy tissue at risk is limited by maximum dose to surrounding critical structures, such as the spinal cord, using the cone collimators does not provide a significant advantage over other modalities. Conclusion: The results show that, depending on the type of sensitivity exhibited by the tissue at risk, use of conical collimators with gated static beam SRS/SBRT on small lung tumors would allow delivery of higher target doses than conventional modalities, while still sparing surrounding normal tissue from damaging dose levels.

Stent outcomes for infrapopliteal arterial occlusive disease

This study aimed to determine if the different stent types used in the treatment of infrapopliteal arterial occlusive disease provide any significant advantage over one another at 6 and 12-month follow-up. Consecutive patients undergoing stenting of infrapopliteal lesions were enrolled into a non-randomised prospective registry and followed-up for 1 year. Outcome measures included binary restenosis, target lesion revascularisation, major amputation, and change in Rutherford-Becker score and ankle-brachial index (ABI).Thirty-three patients were enrolled including four patients with bilateral disease. There were 20 target vessels in the drug-eluting stent (DES) group, 13 target vessels in the balloon-expandable bare metal stent (BE-BMS) group and 14 target vessels in the self expandableb are metal stent (SE-BMS) group. Most of the patients in the study were octogenarians except in the SE-BMS group where the mean age was 73 ± 9 years. At 12 months, seven patients had died (DES = 6, BE-BMS = 1) from cardiac and cancer-related diseases. In-stent and peri-stent binary restenosis were non-statistically different between all three groups. There was a nonstatistically significant trend towards higher target vessel revascularisation in the BE-BMS group. Survival curves in all stent types demonstrated restenosis to occur within the first 6 months post-procedure. There was no significant difference in the change in Rutherford-Becker score or ABI between the groups. No major limb amputations occurred during the 12-month period. In conclusion,we did not detect a significant difference in stent performance between the different stent types used to treat infrapopliteal arterial occlusive disease. The choice of stent did not seem to affect patient survival or major amputation-free survival at 1-year follow-up.

Abstract 1536: Neurropilin-1 high monocytes play an important role in trastuzumab mediated antibody-dependent cellular cytotoxicity in HER2 positive breast cancer cell lines.

Abstract Purpose Neuropilin-1 (NRP-1) was initially characterized as a neuronal receptor for specific secreted members of the semaphorin family involved in axon repulsion. However, it was recently reported to play an important role in the immune system. This study aimed to investigate the role of NRP-1 expression on monocytes in trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) targeting the HER2-positive human breast cell line SKBR3. Methods Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were prepared using Lymphoprep. The cells were stained with fluorescein isothiocyanate (FITC)-conjugated anti-CD14 and allophycocyanin (APC)-conjugated anti-NRP-1 antibodies, and an NRP-1high and NRP-1low monocyte subset was sorted using FACSAria. These cells were used as effector cells in a conventional ADCC assay using SKBR3 as target cells and trastuzumab as an antibody. Target cell cytotoxicity was measured using the LDH cytotoxic test kit. A CD107a degranulation assay was also used to determine the role of NRP-1 expression on monocytes in ADCC. PBMCs were co-cultured with target SKBR3 cells and trastuzumab for 2 h, stained with APC-conjugated anti-NRP-1 and PE-Cy5-conjugated anti-CD107a antibodies, and analyzed by flow cytometry. Results The LDH cytotoxic test revealed significantly higher target cancer cell cytotoxicity in sorted NRP-1 high monocytes (12%) than in NRP-1 low monocytes (4%). Interestingly, microscopic findings showed that most NRP-1 high monocytes covered trastuzumab-treated target cancer cells (showing higher cellular cytotoxicity) while NRP-1 low monocytes did not cover the target cells but changed their morphology from a round to a dendritic shape (showing less cellular cytotoxicity) during ADCC. Moreover, the degranulation assay showed a higher expression of CD107a in NRP-1 high monocytes (17.4%) than in NRP-1 low monocytes (1.16%). Mean fluorescence intensity of CD107a in NRP-1 high and NRP-1 low monocytes was 92.6 and 26.3, respectively. Conclusions These data suggest that NRP-1 high monocytes exhibit higher trastuzumab-mediated ADCC than NRP-1 low monocytes in HER2-positive breast cancer cell lines. It may therefore be possible to differentiate HER2-positive breast cancer patients for whom trastuzumab will be less effective by testing for monocyte NRP-1 expression levels. Citation Format: Kosuke Kawaguchi, Eiji Suzuki, Tomoharu Sugie, Fumiaki Sato, Masakazu Toi. Neurropilin-1 high monocytes play an important role in trastuzumab mediated antibody-dependent cellular cytotoxicity in HER2 positive breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1536. doi:10.1158/1538-7445.AM2013-1536

2118 LACK OF CLINICAL FACTORS INCREASING QUANTITATIVE INTERSTITIAL FIBROSIS AFTER RENAL TRANSPLANTATION UNDER A LOWER TARGET TROUGH STRATEGY OF TACROLIMUS

INTRODUCTION AND OBJECTIVES: Chronic allograft injury is a multi-factorial process based on immunologic and non-immunologic factors, such as elderly donors, acute rejection and immunosuppressive regimens with calcineurin inhibitors. Patients with the CYP3A53/3 genotype (non-expressers) require a lower daily tacrolimus dose than those with the CYP3A51 allele (CYP3A5 expressers) in order to maintain target trough levels. Recently, we reported that interstitial fibrosis (IF) from 0-hour to 1-year post-transplantation increased more in non-expressers than in CYP3A5 expressers with a higher target trough strategy of tacrolimus. Unexpected highly tacrolimus levels in non-expressers might influence the development of IF, despite therapeutic drug monitoring (Miura Y, Transplantation 2011). The present study investigated the increase in IF from 0-hour to 1-year posttransplantation and calculated the risk of developing IF based on clinical characteristics under a lower (medium) target strategy of tacrolimus. METHODS: Ninety-six adult patients receiving living allograft underwent protocol biopsies at 0-hour and 1-year post-transplantation. The blood trough target level of tacrolimus was 15-20 ng/ml within the first, and tapered to less than 8 ng/ml after the fourth week. Quantitative analysis of renal cortical IF was performed using computer-assisted analysis of tissue sections stained with Masson-trichrome. The percentage of IF (%IF) in the allograft cortical region at 0-hour was defined as the baseline, and we calculated the increases in %IF at 1 year. Characteristics of the donor and recipient, clinical events, target trough levels of tacrolimus, CYP3A5 polymorphism, and laboratory data were calculated as risk factors. RESULTS: The mean %IF at 0-hour and 1-year was 11.8u}5.3 % and 14.6u}6.1 %, respectively. The mean increase in %IF from 0-hour to 1-year was 1.38u}0.74. The %IF at 0-hour and 1-year was significantly higher in donors over 60 year-old. The %IF at 0-hour was also higher in donors with eGFR less than 88 ml/min/1.73m2. Although trough levels of tacrolimus were higher in non-expressers than CYP3A5 expressers in the study period, we failed to find any clinical and CYP3A5 genomic factors influenced increased %IF. Moreover, the increased %IF was not associated with death censored graft survival. CONCLUSIONS: The results suggested a lower target trough level of tacrolimus would not influence the development of IF regardless of CYP3A5 polymorphism and graft survival.

In-Hospital Management of Diabetes.

In-Hospital Management of Diabetes.

In-hospital Management of Diabetes

In-hospital Management of Diabetes

Near Infrared Fluorescent Trypsin Stabilized Gold Nanoclusters as Surface Plasmon Enhanced Energy Transfer Biosensor and in Vivo Cancer Imaging Bioprobe

The simplicity of the green-synthesized routine and the availability of surface modification of diverse bioactive molecules make noble metal nanostructures highly suitable as multifunctional biomaterials for biological and biomedical application. Here, we report the preparation of trypsin stabilized gold nanoclusters (try-AuNCs) with near-infrared fluorescence for biosensing heparin based on surface plasmon enhanced energy transfer (SPEET) and folic acid (FA) modified try-AuNCs for in vivo cancer bioimaging. The SPEET/try-AuNCs fluorescence biosensor was designed via heparin mediated energy transfer between try-AuNCs and cysteamine modified gold nanoparticles (cyst-AuNPs). The developed SPEET/try-AuNCs fluorescence biosensor allowed sensitive and selective detection of heparin with a linear range of 0.1-4.0 μg mL(-1) and a detection limit (3s) of 0.05 μg mL(-1). The relative standard deviation for eleven replicate detections of 2.5 μg mL(-1) heparin was 1.1%, and the recoveries of the spiked heparin in human serum samples ranged from 97% to 100%. In addition, folic acid was immobilized on the surface of try-AuNCs to ameliorate the specific affinity of AuNCs for tumors, and the near-infrared fluorescent FA-try-AuNCs were applied for in vivo cancer imaging of high folate receptor (FR) expressing Hela tumor. In vivo study of the dynamic behavior and targeting ability of FA-try-AuNCs probe to Hela tumor bearing mice and normal nude mice validated the high specific affinity of FA-try-AuNCs probe to FR positive tumors. The results show that the prepared try-AuNCs have great potential as multifunctional biomaterials for biosensing biomolecules with SPEET mode and in vivo cancer imaging with high targeting ability.

Effects of Fibrinogen Concentrate as First-line Therapy during Major Aortic Replacement Surgery

Fibrinogen is suggested to play an important role in managing major bleeding. However, clinical evidence regarding the effect of fibrinogen concentrate (derived from human plasma) on transfusion is limited. The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative, targeted, first-line hemostatic therapy in bleeding patients undergoing aortic replacement surgery. In this single-center, prospective, placebo-controlled, double-blind study, patients aged 18 yr or older undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to fibrinogen concentrate or placebo, administered intraoperatively. Study medication was given if patients had clinically relevant coagulopathic bleeding immediately after removal from cardiopulmonary bypass and completion of surgical hemostasis. Dosing was individualized using the fibrin-based thromboelastometry test. If bleeding continued, a standardized transfusion protocol was followed. Twenty-nine patients in the fibrinogen concentrate group and 32 patients in the placebo group were eligible for the efficacy analysis. During the first 24 h after the administration of study medication, patients in the fibrinogen concentrate group received fewer allogeneic blood components than did patients in the placebo group (median, 2 vs. 13 U; P < 0.001; primary endpoint). Total avoidance of transfusion was achieved in 13 (45%) of 29 patients in the fibrinogen concentrate group, whereas 32 (100%) of 32 patients in the placebo group received transfusion (P < 0.001). There was no observed safety concern with using fibrinogen concentrate during aortic surgery. Hemostatic therapy with fibrinogen concentrate in patients undergoing aortic surgery significantly reduced the transfusion of allogeneic blood products. Larger multicenter studies are necessary to confirm the role of fibrinogen concentrate in the management of perioperative bleeding in patients with life-threatening coagulopathy.

Particle size effect on velocity of gold particle embedded laser driven plastic targets

A scheme to enhance the target foil velocity has been investigated for a direct drive inertial fusion target. Polymer PVA (polyvinyl alcohol or (C2H4O)n) target foils of thickness 15-20 mw ere used in plain form and also embedded with gold in the nano-particle (Au-np) or micro-particle (Au-mp) form. Nano- particles were of 20-50nm and micro-particles of 2-3 m in size. 17% higher target velocity was measured for foils embedded with nano-particle gold (Au-np) as compared to targets embedded with micro-particles gold (Au-mp). The weight of gold in both cases was in the range 40-55% of the full target weight (atomic percentage of about 22%). Experiments were performed with the single beam of the Prague Asterix Laser System (PALS) at 0.43 m wavelength (3 of the fundamental wavelength), 120 Joule energy and 300psec pulse duration. Laser intensity on the target was about 10 15 W/cm 2 . A simple model has been proposed to explain the experimental results.

MC8 Peptide-Mediated Her-2 Receptor Targeting Based on PEI-β-CyD as Gene Delivery Vector

A novel vector with high gene delivery efficiency and special cell targeting ability was developed using a good strategy that utilized low molecular weight polyethylenimine (PEI; molecular weight, 600 KDa [PEI600]) cross-linked to β-cyclodextrin (β-CyD) via a facile synthetic route. Human epidermal growth factor receptor 2 (Her-2) are highly expressed in a variety of human cancer cells and are potential targets for cancer therapy. MC8 peptides, which have been proven to combine especially with Her-2 on cell membranes were coupled to PEI-β-CyD using N-succinimidyl-3-(2-pyridyldithio) propionate as a linker. The ratios of PEI600, β-CyD, and peptide were calculated based on proton integral values obtained from the (1)H-NMR spectra of the resulting products. Electron microscope observations showed that MC8-PEI-β-CyD can efficiently condense plasmid DNA (pDNA) into nanoparticles of about 200 nm, and MTT assays suggested the decreased toxicity of the polymer. Experiments on gene delivery efficiency in vitro showed that MC8-PEI-β-CyD/pDNA polyplexes had significantly greater transgene activities than PEI-β-CyD/pDNA in the Skov3 and A549 cells, which positively expressed Her-2, whereas, no such effect was observed in the MCF-7 cells, which negatively expressed Her-2. Our current research indicated that the synthesized nonviral vector shows improved gene delivery efficiency and targeting specificity in Her-2 positive cells.

“Fitting” Makes “Sensing” Simple: Label-Free Detection Strategies Based on Nucleic Acid Aptamers

Nucleic acid aptamers are small sequences of DNA made via in vitro selection techniques to bind targets with high affinity and specificity. The term aptamer derives from the Latin, aptus, meaning "to fit", emphasizing the lock-and-key relationship between aptamers and their binding targets. In 2004, aptamers began to attract researchers' attention as new binding elements for biosensors (i.e. aptasensors). Their advantages over other sensors include a diverse range of possible target molecules, high target affinity, simple synthesis, and ability to form Watson-Crick base pairs. These attributes create an enormous array of possible sensing applications and target molecules, spanning nearly all detection methods and readout techniques. In particular, aptamers provide an opportunity for designing "label-free" sensors, meaning sensors that do not require covalently labeling a signal probe to either the analyte or the recognition element (here, the aptamer). "Label-free" systems previously could only analyze large molecules using a few readout techniques, such as when employing the other recognition elements like antibodies. "Label-free" methods are one of the most effective and promising strategies for faster, simpler, and more convenient detection, since they avoid the expensive and tedious labeling process and challenging labeling reactions, while retaining the highest degree of activity and affinity for the recognition element. "Label-free" sensors are one of the most promising future biosensors. In this Account, we describe our efforts exploring and constructing such label-free sensing strategies based on aptamers. Our methods have included using various readout techniques, employing novel nanomaterials, importing lab-on-a-chip platforms, and improving logical recognition. The resulting sensors demonstrate that aptamers are ideal tools for "label-free" sensors. We divide this Account into three main parts describing three strategies for designing "label-free" sensors: (1) Label-free, separation-free strategies. These include colorimetric sensors based on G-quadruplex-hemin complex, and fluorescent sensors based on fluorescent small molecules, novel conjugated polymers, and metal ion clusters. (2) Label-free, separation-required strategies. In this part, electrochemical sensors are introduced, including sensors with different subtechniques using an electrode array. (3) Logic sensors. Some logic recognition systems are introduced. We emphasize that label-free aptasensors are not merely simple. We hope our introduction illustrates the powerful, flexible, and smart functions of aptamers in carrying out various detection tasks or playing various recognition games. Our work is only a start. We believe this field will bring additional knowledge on general designs, anti-interference, multianalysis, minimization, and auto-operation of aptamer biosensors.