Efficient construction of nonorthogonal localized molecular orbitals in large systems.

Localized molecular orbitals (LMOs) are much more compact representations of electronic degrees of freedom than canonical molecular orbitals (CMOs). The most compact representation is provided by nonorthogonal localized molecular orbitals (NOLMOs), which are linearly independent but are not orthogonal. Both LMOs and NOLMOs are thus useful for linear-scaling calculations of electronic structures for large systems. Recently, NOLMOs have been successfully applied to linear-scaling calculations with density functional theory (DFT) and to reformulating time-dependent density functional theory (TDDFT) for calculations of excited states and spectroscopy. However, a challenge remains as NOLMO construction from CMOs is still inefficient for large systems. In this work, we develop an efficient method to accelerate the NOLMO construction by using predefined centroids of the NOLMO and thereby removing the nonlinear equality constraints in the original method ( J. Chem. Phys. 2004 , 120 , 9458 and J. Chem. Phys. 2000 , 112 , 4 ). Thus, NOLMO construction becomes an unconstrained optimization. Its efficiency is demonstrated for the selected saturated and conjugated molecules. Our method for fast NOLMO construction should lead to efficient DFT and NOLMO-TDDFT applications to large systems.

Pulsating tandem microbubble for localized and directional single-cell membrane poration.

The interaction of laser-generated tandem microbubble (maximum diameter of about 50  μm) with single (rat mammary carcinoma) cells is investigated in a 25-μm liquid layer. Antiphase and coupled oscillation of the tandem microbubble leads to the formation of alternating, directional microjets (with max microstreaming velocity of 10  m/s) and vortices (max vorticity of 350 000  s{-1}) in opposite directions. Localized and directional membrane poration (200 nm to 2  μm in pore size) can be produced by the tandem microbubble in an orientation and proximity-dependent manner, which is absent from a single oscillating microbubble of comparable size and at the same stand-off distance.

Pharmacological targeting of the mitochondrial phosphatase PTPMT1.

The dual-specificity protein tyrosine phosphatases (PTPs) play integral roles in the regulation of cell signaling. There is a need for new tools to study these phosphatases, and the identification of inhibitors potentially affords not only new means for their study, but also possible therapeutics for the treatment of diseases caused by their dysregulation. However, the identification of selective inhibitors of the protein phosphatases has proven somewhat difficult. PTP localized to mitochondrion 1 (PTPMT1) is a recently discovered dual-specificity phosphatase that has been implicated in the regulation of insulin secretion. Screening of a commercially available small-molecule library yielded alexidine dihydrochloride, a dibiguanide compound, as an effective and selective inhibitor of PTPMT1 with an in vitro concentration that inhibits response by 50% of 1.08 microM. A related dibiguanide analog, chlorhexidine dihydrochloride, also significantly inhibited PTPMT1, albeit with lower potency, while a monobiguanide analog showed very weak inhibition. Treatment of isolated rat pancreatic islets with alexidine dihydrochloride resulted in a dose-dependent increase in insulin secretion, whereas treatment of a pancreatic beta-cell line with the drug affected the phosphorylation of mitochondrial proteins in a manner similar to genetic inhibition of PTPMT1. Furthermore, knockdown of PTPMT1 in rat islets rendered them insensitive to alexidine dihydrochloride treatment, providing evidence for mechanism-based activity of the inhibitor. Taken together, these studies establish alexidine dihydrochloride as an effective inhibitor of PTPMT1, both in vitro and in cells, and support the notion that PTPMT1 could serve as a pharmacological target in the treatment of type II diabetes.

Pairing QuantiFERON gold in-tube with opt-out HIV testing in a tuberculosis contact investigation in the Southeastern United States.

Knowing one's HIV status is particularly important in the setting of recent tuberculosis (TB) exposure. Blood tests for assessment of tuberculosis infection, such as the QuantiFERON Gold in-tube test (QFT; Cellestis Limited, Carnegie, Victoria, Australia), offer the possibility of simultaneous screening for TB and HIV with a single blood draw. We performed a cross-sectional analysis of all contacts to a highly infectious TB case in a large meatpacking factory. Twenty-two percent were foreign-born and 73% were black. Contacts were tested with both tuberculin skin testing (TST) and QFT. HIV testing was offered on an opt-out basis. Persons with TST >or=10 mm, positive QFT, and/or positive HIV test were offered latent TB treatment. Three hundred twenty-six contacts were screened: TST results were available for 266 people and an additional 24 reported a prior positive TST for a total of 290 persons with any TST result (89.0%). Adequate QFT specimens were obtained for 312 (95.7%) of persons. Thirty-two persons had QFT results but did not return for TST reading. Twenty-two percent met the criteria for latent TB infection. Eighty-eight percent accepted HIV testing. Two (0.7%) were HIV seropositive; both individuals were already aware of their HIV status, but one had stopped care a year previously. None of the HIV-seropositive persons had latent TB, but all were offered latent TB treatment per standard guidelines. This demonstrates that opt-out HIV testing combined with QFT in a large TB contact investigation was feasible and useful. HIV testing was also widely accepted. Pairing QFT with opt-out HIV testing should be strongly considered when possible.

Contemporary results of focal therapy for prostate cancer using cryoablation.

The concept of focal therapy is rapidly evolving and gaining popularity from both physician and patient perspectives. We review the rationale, candidate selection, and results of the first clinical studies of focal cryoablation for selected patients with low volume and low- to low-moderate-risk features of prostate cancer as an alternative to whole-gland treatment. In spite of improved understanding of the tumor biology of early stage disease, we currently have limited tools to select appropriate patients with low- to low-moderate risk unifocal or unilateral prostate cancer who may be amenable to focal therapy. From a technical point, a number of ablative treatment options for focal therapy are available, with cryoablation having the most clinical experience. Recently, several reports have been published from single and multi-institutional studies that discuss focal therapy as a reasonable balance between cancer control and quality-of-life outcomes. Retrospective pathologic data from large prostatectomy series, however, do not clearly reveal valid and reproducible criteria to select appropriate candidates for focal cryoablation because of the complexity of tumorigenesis in early stage disease. At this time, a more feasible option remains hemiablation of the prostate with reasonable certainty about the absence of clinically significant cancer lesion(s) on the contralateral side of the prostate based on three-dimensional transperineal prostate biopsy mapping studies. Minimally invasive, parenchyma-preserving cryoablation can be considered as a potential feasible option in the treatment armamentarium of early stage, localized prostate cancer in appropriately selected candidates. There is a need to further test this technique in randomized, multicenter clinical trials.

Prostate biopsy in selecting candidates for hemiablative focal therapy.

Focal therapy (FT) for the management of clinically localized prostate cancer (PCa) is growing from a concept to reality because of increased interest of both patients and physicians. Selection protocols, however, are yet to be established. We discuss the role of prostate biopsy in candidate selection for FT and highlight the different strategies and technical aspects of the use of prostate biopsy in this setting. In our opinion, prostate biopsy plays a major role in the selection process and tailoring appropriate treatment strategy to the patient. FT necessitates dedicated biopsy schemes that would reliably predict the extent, nature, and location of PCa in selected patients. Currently, there is insufficient scientific evidence to propose a specific biopsy scheme that could fit every candidate, providing accurate characterization of the disease in the individual patient. Further research is necessary to establish solid selection protocols that would reliably identify appropriate candidates for FT of PCa.

Porcine endothelial cells cocultured with smooth muscle cells became procoagulant in vitro.

Endothelial cell (EC) seeding represents a promising approach to provide a nonthrombogenic surface on vascular grafts. In this study, we used a porcine EC/smooth muscle cell (SMC) coculture model that was previously developed to examine the efficacy of EC seeding. Expression of tissue factor (TF), a primary initiator in the coagulation cascade, and TF activity were used as indicators of thrombogenicity. Using immunostaining, primary cultures of porcine EC showed a low level of TF expression, but a highly heterogeneous distribution pattern with 14% of ECs expressing TF. Quiescent primary cultures of porcine SMCs displayed a high level of TF expression and a uniform pattern of staining. When we used a two-stage amidolytic assay, TF activity of ECs cultured alone was very low, whereas that of SMCs was high. ECs cocultured with SMCs initially showed low TF activity, but TF activity of cocultures increased significantly 7-8 days after EC seeding. The increased TF activity was not due to the activation of nuclear factor kappa-B on ECs and SMCs, as immunostaining for p65 indicated that nuclear factor kappa-B was localized in the cytoplasm in an inactive form in both ECs and SMCs. Rather, increased TF activity appeared to be due to the elevated reactive oxygen species levels and contraction of the coculture, thereby compromising the integrity of EC monolayer and exposing TF on SMCs. The incubation of cocultures with N-acetyl-cysteine (2 mM), an antioxidant, inhibited contraction, suggesting involvement of reactive oxygen species in regulating the contraction. The results obtained from this study provide useful information for understanding thrombosis in tissue-engineered vascular grafts.

Cost of wind energy: comparing distant wind resources to local resources in the midwestern United States.

The best wind sites in the United States are often located far from electricity demand centers and lack transmission access. Local sites that have lower quality wind resources but do not require as much power transmission capacity are an alternative to distant wind resources. In this paper, we explore the trade-offs between developing new wind generation at local sites and installing wind farms at remote sites. We first examine the general relationship between the high capital costs required for local wind development and the relatively lower capital costs required to install a wind farm capable of generating the same electrical output at a remote site,with the results representing the maximum amount an investor should be willing to pay for transmission access. We suggest that this analysis can be used as a first step in comparing potential wind resources to meet a state renewable portfolio standard (RPS). To illustrate, we compare the cost of local wind (∼50 km from the load) to the cost of distant wind requiring new transmission (∼550-750 km from the load) to meet the Illinois RPS. We find that local, lower capacity factor wind sites are the lowest cost option for meeting the Illinois RPS if new long distance transmission is required to access distant, higher capacity factor wind resources. If higher capacity wind sites can be connected to the existing grid at minimal cost, in many cases they will have lower costs.

Excitation of highly conjugated (porphinato)palladium(II) and (porphinato)platinum(II) oligomers produces long-lived, triplet states at unit quantum yield that absorb strongly over broad spectral domains of the NIR.

Transient dynamical studies of bis[(5,5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)palladium(II)]ethyne (PPd(2)), 5,15-bis{[(5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)palladium(II)]ethynyl}(10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)palladium(II) (PPd(3)), bis[(5,5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)platinum(II)]ethyne (PPt(2)), and 5,15-bis{[(5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)platinum(II)]ethynyl}(10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)platinum(II) (PPt(3)) show that the electronically excited triplet states of these highly conjugated supermolecular chromophores can be produced at unit quantum yield via fast S(1) → T(1) intersystem crossing dynamics (τ(isc): 5.2-49.4 ps). These species manifest high oscillator strength T(1) → T(n) transitions over broad NIR spectral windows. The facts that (i) the electronically excited triplet lifetimes of these PPd(n) and PPt(n) chromophores are long, ranging from 5 to 50 μs, and (ii) the ground and electronically excited absorptive manifolds of these multipigment ensembles can be extensively modulated over broad spectral domains indicate that these structures define a new precedent for conjugated materials featuring low-lying π-π* electronically excited states for NIR optical limiting and related long-wavelength nonlinear optical (NLO) applications.

Leveraging nanoscale plasmonic modes to achieve reproducible enhancement of light.

The strongly enhanced and localized optical fields that occur within the gaps between metallic nanostructures can be leveraged for a wide range of functionality in nanophotonic and optical metamaterial applications. Here, we introduce a means of precise control over these nanoscale gaps through the application of a molecular spacer layer that is self-assembled onto a gold film, upon which gold nanoparticles (NPs) are deposited electrostatically. Simulations using a three-dimensional finite element model and measurements from single NPs confirm that the gaps formed by this process, between the NP and the gold film, are highly reproducible transducers of surface-enhanced resonant Raman scattering. With a spacer layer of roughly 1.6 nm, all NPs exhibit a strong Raman signal that decays rapidly as the spacer layer is increased.

Plasmon-induced electrical conduction in molecular devices.

Metal nanoparticles (NPs) respond to electromagnetic waves by creating surface plasmons (SPs), which are localized, collective oscillations of conduction electrons on the NP surface. When interparticle distances are small, SPs generated in neighboring NPs can couple to one another, creating intense fields. The coupled particles can then act as optical antennae capturing and refocusing light between them. Furthermore, a molecule linking such NPs can be affected by these interactions as well. Here, we show that by using an appropriate, highly conjugated multiporphyrin chromophoric wire to couple gold NP arrays, plasmons can be used to control electrical properties. In particular, we demonstrate that the magnitude of the observed photoconductivity of covalently interconnected plasmon-coupled NPs can be tuned independently of the optical characteristics of the molecule-a result that has significant implications for future nanoscale optoelectronic devices.

Reformulating time-dependent density functional theory with non-orthogonal localized molecular orbitals.

Time-dependent density functional theory (TDDFT) has broad application in the study of electronic response, excitation and transport. To extend such application to large and complex systems, we develop a reformulation of TDDFT equations in terms of non-orthogonal localized molecular orbitals (NOLMOs). NOLMO is the most localized representation of electronic degrees of freedom and has been used in ground state calculations. In atomic orbital (AO) representation, the sparsity of NOLMO is transferred to the coefficient matrix of molecular orbitals (MOs). Its novel use in TDDFT here leads to a very simple form of time propagation equations which can be solved with linear-scaling effort. We have tested the method for several long-chain saturated and conjugated molecular systems within the self-consistent charge density-functional tight-binding method (SCC-DFTB) and demonstrated its accuracy. This opens up pathways for TDDFT applications to large bio- and nano-systems.

Jamming for a 2D granular material

This paper focuses on the nature of jamming, as seen in two-dimensional frictional granular systems consisting of photoelastic particles. The photoelastic technique is unique at this time, in its capability to provide detailed particle-scale information on forces and kinematic quantities such as particle displacements and rotations. These experiments first explore isotropic stress states near point J through measurements of the mean contact number per particle, Z, and the pressure, P as functions of the packing fraction, . In this case, the experiments show some but not all aspects of jamming, as expected on the basis of simulations and models that typically assume conservative, hence frictionless, forces between particles. Specifically, there is a rapid growth in Z, at a reasonable which we identify with as c. It is possible to fit Z and P, to power law expressions in - c above c, and to obtain exponents that are in agreement with simulations and models. However, the experiments differ from theory on several points, as typified by the rounding that is observed in Z and P near c. The application of shear to these same 2D granular systems leads to phenomena that are qualitatively different from the standard picture of jamming. In particular, there is a range of packing fractions below c, where the application of shear strain at constant leads to jammed stress-anisotropic states, i.e. they have a non-zero shear stress, τ. The application of shear strain to an initially isotropically compressed (hence jammed) state, does not lead to an unjammed state per se. Rather, shear strain at constant first leads to an increase of both τ and P. Additional strain leads to a succession of jammed states interspersed with relatively localized failures of the force network leading to other stress-anisotropic states that are jammed at typically somewhat lower stress. The locus of jammed states requires a state space that involves not only and τ, but also P. P, τ, and Z are all hysteretic functions of shear strain for fixed . However, we find that both P and τ are roughly linear functions of Z for strains large enough to jam the system. This implies that these shear-jammed states satisfy a Coulomb like-relation, τ = μP. © 2010 The Royal Society of Chemistry.

Measuring morphological features using light-scattering spectroscopy and Fourier-domain low-coherence interferometry.

We present measurements of morphological features in a thick turbid sample using light-scattering spectroscopy (LSS) and Fourier-domain low-coherence interferometry (fLCI) by processing with the dual-window (DW) method. A parallel frequency domain optical coherence tomography (OCT) system with a white-light source is used to image a two-layer phantom containing polystyrene beads of diameters 4.00 and 6.98 mum on the top and bottom layers, respectively. The DW method decomposes each OCT A-scan into a time-frequency distribution with simultaneously high spectral and spatial resolution. The spectral information from localized regions in the sample is used to determine scatterer structure. The results show that the two scatterer populations can be differentiated using LSS and fLCI.

Intensification of summer rainfall variability in the southeastern United States during recent decades

The variability of summer precipitation in the southeastern United States is examined in this study using 60-yr (1948-2007) rainfall data. The Southeast summer rainfalls exhibited higher interannual variability with more intense summer droughts and anomalous wetness in the recent 30 years (1978-2007) than in the prior 30 years (1948-77). Such intensification of summer rainfall variability was consistent with a decrease of light (0.1-1 mm day-1) and medium (1-10 mm day-1) rainfall events during extremely dry summers and an increase of heavy (.10 mm day-1) rainfall events in extremely wet summers. Changes in rainfall variability were also accompanied by a southward shift of the region of maximum zonal wind variability at the jet stream level in the latter period. The covariability between the Southeast summer precipitation and sea surface temperatures (SSTs) is also analyzed using the singular value decomposition (SVD) method. It is shown that the increase of Southeast summer precipitation variability is primarily associated with a higher SST variability across the equatorial Atlantic and also SST warming in the Atlantic. © 2010 American Meteorological Society.