Low-density Targets Research Articles

Reaching Un-Drugable Intracellular Targets with the Long Arm of Antibodies

Reaching Un-Drugable Intracellular Targets with the Long Arm of Antibodies

Hexagonally Arranged Nanopore Film Fabricated via Selective Etching by 172-nm Vacuum Ultraviolet Light Irradiation

Highly ordered nanopore arrays were successfully fabricated using poly(ethylene oxide) (PEO) and polymethacrylate with azobenzene mesogen in side chains [PMA(Az)] block copolymer film based on irradiation of 172-nm vacuum ultraviolet (VUV) light. The block copolymer forms a highly ordered microphase-separated film with perpendicularly oriented PEO cylinders just by thermal annealing through a self-assembling process. We found that the etching rate of the PEO homopolymer was much higher than that of the PMA(Az) homopolymer at a chamber pressure of 102 Pa of atmosphere under VUV irradiation. The etching rate of the PEO component in the two systems of microphase separation and macrophase separation of the homopolymer blend crucially depended on the feature size of phase separation. In the PEO selective etching process of the block copolymer film, the water-contact angle of the film dramatically increased due to elimination of hydrophilic PEO. The resulting nanopore array film will be useful for low-density target materials.

The influence of target material and thickness on proton energy and angular distribution

The paper has studied the influence of target material and thickness on energy and angular distributions of the protons generated by using an 800 nm, 60 fs, 0.24 J laser pulse to irradiate solid target foils. The results show that the initial density and thickness of the targets will affect the formation of the acceleration sheath fields in the target normal direction. For the same target thickness, using lower density target materials can obtain a higher proton maximum energy. However, lower density targets tend to be deformed due to the shock waves launched by the laser pulses, making the proton spatial distribution more divergent.

Laser ion acceleration in the high laser energy and high laser intensity regimes

New laser facilities able to deliver either ultra high energy short pulses or ultra high intensity pulses are being constructed and will open new and exciting opportunities for laser ion acceleration. The interaction of a high intensity short pulse with underdense, near-critical and overdense targets has been studied using 2D Particle-In-Cell simulations in these regimes. In the ultra high energy regime, proton beams with maximum energies of hundreds of MeV and a high number of high energy protons could be accelerated using thin solid foils or low density targets. In the ultra high intensity regime, radiation losses will start affecting laser ion acceleration using thin overdense targets for intensities higher than 10 22 W/cm 2 , and produce very energetic ions.

Penetration into low-density media: In situ observation of penetration process of various projectiles

In order to understand the penetration process of projectiles into lower-density targets, we carry out hypervelocity impact experiments using low-density (60mgcm−3) aerogel targets and various types of projectiles, and observe the track formation process in the targets using a high-speed camera. A carrot shaped track, a bulbous, and a “hybrid” one consisting of bulbous and thin parts, are formed. The results of the high-speed camera observations reveal the similarity and differences on the temporal evolution of the penetration depth and maximum diameter of these tracks. At very early stages of an impact, independent of projectile type, the temporal penetration depth is described by hydrodynamic models for the original projectiles. Afterward, when the breakup of projectiles does not occur, intact projectiles continue to penetrate the aerogels. In the case of the breakup of projectiles, the track expands with a velocity of about a sound velocity of the aerogel at final stages. If there are large fragments, they penetrate deeper and the tracks become a hybrid type. The penetration of the large fragments is described by hydrodynamic models. Based on these results, we discuss the excavation near the impact point by shock waves.

Copper-62 Labeled ReCCMSH Peptide Analogs for Melanoma PET Imaging

High-specific activity radiolabeled melanocortin peptide preparations are necessary for optimal melanoma imaging due to the relatively low number of melanocortin-1 receptors (MC1-Rs) per tumor cell. In this study, a one-step synthesis of 62Cu-labeled MC1-R targeting peptide Re(Arg11)CCMSH was developed, which yielded high specific activity radiolabeled peptide preparations that required no post-labeling purification. DOTA and NOTA conjugated Re(Arg11)CCMSH peptides were synthesized and examined for 62Cu radiolabeling and cell binding properties. Biodistribution and PET imaging studies were performed to assess the in vivo tumor targeting and imaging characteristics of the optimal radiolabeled peptide. Melanoma cell binding affinities for NOTA-, NOTA-GGG-, and NOTA-GSG- conjugated Re(Arg11)CCMSH were determined to be 1.3×10-9 M, 1.9×10-9 M and 6.0×10-9 M. The 62Cu radiolabeling efficiencies of DOTA- and NOTA- conjugated Re(Arg11)CCMSH analogs were 30% and > 98% after 2 min at 24° C, while 0.5 μg of NOTA-GGG-peptide could be labeled to > 95% with a maximum specific activity of 138 Ci/μmol. Tumor uptake of 62Cu- NOTA-GGG-Re(Arg11)CCMSH in B16/F1 melanoma bearing mice was 4.65±0.48% ID/g and 9.43±2.69% ID/g at 20 and 40 min post injection and was visualized by PET imaging. High specific activity 62Cu-NOTA-GGG-Re(Arg11)CCMSH was prepared in a one-step procedure at 24°C in 6 min. 62Cu-NOTA-GGG-Re(Arg11)CCMSH exhibited MC1-R selective binding and rapid tumor uptake in B16/F1 melanoma bearing mice that was confirmed by PET imaging studies. High specific activity 62Cu from a 62Zn/62Cu generator coupled with simple one step radiolabeling procedures makes 62Cu an attractive radionuclide for PET imaging of low-density receptor targets.

Assessment of Low-Density Lipoprotein Targets

The clinical importance of lowering of total cholesterol and low-density lipoprotein cholesterol (LDL-C) to decrease cardiovascular (CV) risk has been verified over many years starting with significant support in 1984 of the then previous lipid hypothesis. Significant support of this hypothesis began that year with publication of the Lipid Research Clinic study. Since then, multiple other studies including outcomes studies have established the value of LDL-C reduction in decreasing CV risk. In addition, multiple other factors such as inflammation, endothelial dysfunction, nitric oxide, antioxidant properties, and plaque stabilization appear important for modifying CV risk and possible favorable alterations by medications such as statins must be considered. Nevertheless, reduction of LDL-C has well-established value and is being accepted by clinicians as a major guideline for CV disease prevention. However, there are still problems with adherence by many clinicians to CV risk modification. Therefore, abandoning LDL-C reduction as a target, as has been advocated by some, appears premature and contraindicated. A strategy of LDL-C reduction in no way interferes with increased understanding of the complexities of atherosclerosis and new approaches to CV disease prevention as they become supported by outcomes studies.

Acceleration of laser-driven ion bunch from double-layer thin foils

Generation of monoenergetic ion bunch from a double-layer thin-foil target irradiated by an intense linearly polarized laser pulse is investigated using two-dimensional particle-in-cell simulation. The protons in the front low-density hydrogen target layer accelerated by the space-charge field of the laser-driven hot electrons can penetrate through the high-Z high-mass and high-density ion layer, resulting in an energetic proton bunch. A part of the latter is further accelerated by the space-charge field of the hot electrons in the vacuum behind the high-Z ion layer. With this scheme, quasi-monoenergetic proton bunches can be produced using presently available laser pulses of moderate contrast and duration.

How Accurate Are 3 Risk Prediction Models in US Women?

Cardiovascular disease (CVD) is the leading cause of death for US women, and nearly two thirds who died suddenly of CVD had no previous symptoms.1 Therefore, it is of great importance to identify “at-risk” women early, so that effective primary prevention strategies can be instituted. A universal recommendation of prevention guidelines is that all asymptomatic women should undergo a global risk assessment.2 Article see p 1748 The Adult Treatment Panel III (ATP-III) of the National Cholesterol Education Program set thresholds for lipid treatment based on one's predicted 10-year risk for a hard coronary heart disease (CHD) event (myocardial infarction or CHD death) using a modified Framingham risk score (FRS).3 There are limitations, however, with use of the ATP-III model for CVD prediction in women. The ATP-III version predicts “hard” CHD events but not angina or revascularizations, even if such revascularizations are performed to manage an acute coronary syndrome. Yet women are more likely to experience “soft” CHD events or strokes than men. Moreover, a single laboratory measurement does not reflect lipid values over a woman's lifetime. The FRS does not take into account family history of premature CHD, a well-established independent risk factor for CHD events.4 Also, because stroke accounts for a higher proportion of CVD events than CHD in women before age 75 years,1 we believe that total CVD risk should be the outcome for prediction and preventive strategies. Indeed, that is the conclusion of the 2011 American Heart Association CVD prevention guidelines for women.5 Furthermore, the FRS only predicts 10-year risk, whereas for women, the issue is most often “lifetime” risk. The Third National Health and Nutrition Examination Survey found that among women without a history of CHD or diabetes, 92% of those aged 60 to 69 years and >98% aged <59 …

Three Reasons to Abandon Low-Density Lipoprotein Targets

The updated clinical guidelines for cholesterol testing and management (Adult Treatment Panel (ATP) IV) from the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults are under development and due to be published in 2012. These influential guidelines are organized and funded by the National Heart, Lung, and Blood Institute (NHLBI) and carry the imprimatur of the federal government. In this iteration, the NHLBI has a stated goal of integrating its set of Cardiovascular Risk Reduction guidelines.1 A primary focus of the previous version of the guidelines, ATP III, was a strategy of treating patients to target low-density lipoprotein (LDL) cholesterol levels. ATP III stated that “recent clinical trials robustly show that LDL-lowering therapy reduces risk for CHD. For these reasons, ATP III continues to identify elevated LDL cholesterol as the primary target of cholesterol-lowering therapy. As a result, the primary goals of therapy and the cutpoints for initiating treatment are stated in terms of LDL.” This reasoning, however, diverged from the clinical evidence, recommending an approach that was not tested in any clinical trial. Outcomes research promotes the need to demonstrate benefit before making recommendations for medical intervention.2,3 In that spirit, we present an open letter to the ATP IV Committee that provides the rationale for why the new guidelines should abandon the treat-to-target paradigm. Dear ATP IV Committee, We are writing to encourage you to abandon the paradigm of treating patients to LDL targets, a change that will better align ATP IV with current clinical evidence. Changing long-held beliefs is never easy, even when the need for change is based on strong evidence. Change is especially difficult when prior beliefs are firmly embedded in culture, accepted as dogma, and codified in books, articles, guidelines, public service announcements, and performance measures. …

Control of nitromethane photoionization efficiency with shaped femtosecond pulses

The applicability of adaptive femtosecond pulse shaping is studied for achieving selectivity in the photoionization of low-density polyatomic targets. In particular, optimal dynamic discrimination (ODD) techniques exploit intermediate molecular electronic resonances that allow a significant increase in the photoionization efficiency of nitromethane with shaped near-infrared femtosecond pulses. The intensity bias typical of high-photon number, nonresonant ionization is accounted for by reference to a strictly intensity-dependent process. Closed-loop adaptive learning is then able to discover a pulse form that increases the ionization efficiency of nitromethane by ∼150%. The optimally induced molecular dynamics result from entry into a region of parameter space inaccessible with intensity-only control. Finally, the discovered pulse shape is demonstrated to interact with the molecular system in a coherent fashion as assessed from the asymmetry between the response to the optimal field and its time-reversed counterpart.

Use of a Treatment Optimization Algorithm Involving Statin-Ezetimibe Combination Aids in Achievement of Guideline-Based Low-Density Lipoprotein Targets in Patients With Dyslipidemia at High Vascular Risk Guideline-Based Undertaking to Improve Dyslipidemia Management in Canada (GUIDANC)

Background Despite the well-established benefits of strategies to reduce low-density lipoprotein cholesterol (LDL-C), many patients fail to achieve the guideline recommended targets. The objective of this study was to evaluate the impact of an enhanced 26-week algorithm-based treatment optimization strategy, involving titration of statin monotherapy and/or combination therapy with statin and ezetimibe, on achievement of guideline-based LDL-C targets in patients at high risk for atherosclerotic disease. Methods and Results In this national (172-physician) quality enhancement research initiative involving 2334 Canadian men and women (median age, 65 years) at high vascular risk who were not at the guideline-recommended LDL-C target despite statin therapy, 36.6% and 45.5% of patients achieved an LDL-C <2.0 mmol/L at visit 2 and visit 3, respectively, using the treatment optimization algorithm. The percentage of patients achieving the 2009 Canadian Cardiovascular Society (CCS)-recommended target of either LDL-C <2.0 mmol/L or a 50% or greater reduction from baseline increased from 6.8% at visit 1 to 43.3% at visit 2 and to 52.1% at visit 3. Attainment of LDL-C targets increased significantly with consecutive visits ( P < .001). Use of ezetimibe in combination with statin therapy was associated with greater target achievement. Conclusions Use of a structured treatment optimization algorithm, based on titration of statin dosages and incorporation of ezetimibe therapy when required, enabled the majority of high-risk patients to achieve guideline-recommended targets, thereby narrowing the care gap that exists in dyslipidemia management.

Ultrashort-laser-pulse absorption with spatial dispersion and nonlocal transport effects

We study ultrashort-laser-pulse absorption and plasma heating at a sharp plasma–vacuum interface using advanced models for all-range plasma permittivity and nonlocal heat transport. The electron response includes both collisional and collisionless dissipative effects in the plasma of an arbitrary ion charge. We show that nonlocal electron heat transport is important for correct determination of the value of electron temperature and spatial temperature profile. Nonlocal electron heat flux comes into play after electrons heat up to temperatures of the order of 1 keV and to temperatures several times less for low-density targets.

Comparative analysis of laser-triggered proton generation from overdense and low-density targets

Abstract Based on 3D particle-in-cell (PIC) simulations a comparative analysis of laser-triggered proton generation from the interaction of short high-intensity laser pulses with ultrathin foils and dense gas jets has been performed. It has been shown that for ultra-relativistic laser intensities the use of low-density targets with near critical density (aerogel or dense gas jet) has no advantage in comparison with ultrathin foils in terms of maximum proton energy and spectrum quality. Utilization of mass-limited foils with submicron thickness demonstrates even greater superiority for overdense targets and allows one to produce monoenergetic proton beams with energies of hundreds of mega-electron-volts by using high-contrast laser pulses with energies of the order of tens of Joules.

Monolithic and Low-Density (

This paper introduces examples of low-density (<50 mg/cm3) metal oxide targets using the electrospinning technique. Millimeter-sized targets of vanadium oxide and copper oxide were fabricated successfully. Low-density materials give well-controlled low-density plasma to produce an optically thin plasma. The advantage of the electrospinning sol-gel method is that the microstructure of the metal oxide fiber sheet can be designed and fabricated to meet the demand of the target in a very convenient way with mass production. The obtained low-density metal oxide can be used for the laser target to generate extreme ultraviolet light and X-rays.

Systematic investigation of self-absorption and conversion efficiency of 6.7 nm extreme ultraviolet sources

We have investigated the dependence of the spectral behavior and conversion efficiencies of rare-earth plasma extreme ultraviolet sources with peak emission at 6.7 nm on laser wavelength and the initial target density. The maximum conversion efficiency was 1.3% at a laser intensity of 1.6×1012 W/cm2 at an operating wavelength of 1064 nm, when self-absorption was reduced by use of a low initial density target. Moreover, the lower-density results in a narrower spectrum and therefore improved spectral purity. It is shown to be important to use a low initial density target and/or to produce low electron density plasmas for efficient extreme ultraviolet sources when using high-Z targets.

Generation and optimization of electron currents along the walls of a conical target for fast ignition

The interaction of an ultraintense laser pulse with a conical target is studied by means of numerical particle-in-cell simulations in the context of fast ignition. The divergence of the fast electron beam generated at the tip of the cone has been shown to be a crucial parameter for the efficient coupling of the ignition laser pulse to the precompressed fusion pellet. In this paper, we demonstrate that a focused hot electron beam is produced at the cone tip, provided that electron currents flowing along the surfaces of the cone sidewalls are efficiently generated. The influence of various interaction parameters over the formation of these wall currents is investigated. It is found that the strength of the electron flows is enhanced for high laser intensities, low density targets, and steep density gradients inside the cone. The hot electron energy distribution obeys a power law for energies of up to a few MeV, with the addition of a high-energy Maxwellian tail.

A model of the energy transport in turbulent laser plasma of porous targets

A physical–mathematical model of the interaction of high-power laser pulses with a low-density porous target has been proposed. Such a plasma is strongly inhomogeneous and turbulent. The direct computer modeling of three-dimensional (3D) vortex flows in such a plasma is a very laborious process for modern supercomputers. We have developed a single-parameter model of energy transport in a turbulent laser plasma. 2D numerical simulations have been carried out for the modeling of ‘hydrothermal wave’ expansion in such a plasma using the 2D Lagrange code ATLANT-C. There was good agreement between the numerical results and the experimental data from the Prague Asterix Laser System (PALS) facility. We discuss various different applications of such porous targets in modern high-energy density physics.

Laser-produced plasmas as unique x-ray souces for industry and astrophysics

Laser produced plasma is one of the brilliant x-ray source that has unique capabilities for use in a wide range of science. Here we describe two examples of laser-produced plasma x-ray source application; one is for the semiconductor device industry and the other is for the astronomy. Extreme ultraviolet (EUV) light sources for microlithography are receiving much attention as an industrial application of laser-produced x-ray source. High power and clean EUV light source, 13.5 nm of wavelength, is developed for mass-production of next generation semiconductor devices. Highest EUV conversion efficiency of 4% has been attained by using low-density and minimum-mass tin targets produced by laser-driven explosion of micro-droplet. In addition, it was recently demonstrated that laser-produced x-ray source is very useful to simulate x-ray astronomical phenomena in the laboratory. A 0.5-keV Planckian x-ray source was created with laser driven implosion for producing non-local-thermodynamical-equilibrium (non-LTE) photoionized plasmas, which is a key to understand astronomical compact objects. Laboratory experiment of non-LTE photoionized plasma offers novel test bed for validation and verification of computational codes used in x-ray astronomy.

Proton radiography of a shock-compressed target

In this paper we report on the radiography of a shock-compressed target using laser produced proton beams. A low-density carbon foam target was shock compressed by long pulse high-energy laser beams. The shock front was transversally probed with a proton beam produced in the interaction of a high intensity laser beam with a gold foil. We show that from radiography data, the density profile in the shocked target can be deduced using Monte Carlo simulations. By changing the delay between long and short pulse beams, we could probe different plasma conditions and structures, demonstrating that the details of the steep density gradient can be resolved. This technique is validated as a diagnostic for the investigation of warm dense plasmas, allowing an in situ characterization of high-density contrasted plasmas.