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Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase-polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests (neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR. With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus-based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection. [ABSTRACT FROM AUTHOR]

Zinc-finger protein transcription factors (ZFP TFs) can be designed to control the expression of any desired target gene, and thus provide potential therapeutic tools for the study and treatment of disease. Here we report that a ZFP TF can repress target gene expression with single-gene specificity within the human genome. A ZFP TF repressor that binds an 18-bp recognition sequence within the promoter of the endogenous CHK2 gene gives a >10-fold reduction in CHK2 mRNA and protein. This level of repression was sufficient to generate a functional phenotype, as demonstrated by the loss of DNA damage-induced CHK2-dependent p53 phosphorylation. We determined the specificity of repression by using DNA microarrays and found that the ZFP TF repressed a single gene (CHK2) within the monitored genome in two different cell types. These data demonstrate the utility of ZFP TFs as precise tools for target validation, and highlight their potential as clinical therapeutics. [ABSTRACT FROM AUTHOR]

Thin-layer chromatography and infrared reflectance spectroscopy were compared as methods for measuring sebum composition. Solutions of varying known Concentrations of free fatty acids and triglycerides were analyzed by both methods. Skin surface lipid samples were similarly analyzed. Infrared spectroscopy produced more variable data than thin-layer chromatography with photodensitometry. This was particularly true at low concentrations of free fatty acids. It is concluded that thin-layer chromatography with photodensitometry is a more accurate method for the measurement of sebum composition. [ABSTRACT FROM AUTHOR]

If the apparent contact angle (ACA) of superhydrophobic materials could be significantly affected by drop volume, it would not be reliable to use ACA as an important index to evaluate the wettability of superhydrophobic materials. In order to explore the effect of drop volume on the ACA of hierarchical structured superhydrophobic surfaces, two kinds of hierarchical structured superhydrophobic surfaces, natural lotus leaf surface and superhydrophobic coating, were used for experimental analysis. In addition, a physical model of ACA considering drop volume was established. And the relationship curve between drop volume and ACA was calculated. The experiment and simulation results show that for each kind of drop, the volume has no significant effect on the ACA of hierarchical structured superhydrophobic surfaces. And the ACA can reflect the wettability of the superhydrophobic material effectively. [ABSTRACT FROM AUTHOR]

Abstract: Air and surface chlorpyrifos residues were measured for 24 hours following a 0.5 percent Dursban(R) broadcast application for fleas inside a residence. Two of the three treated rooms were ventilated following application. Maximum air concentrations were measured 3-7 hours post-application. Peak concentrations in the infant breathing zone were 94 µ g/m&sup 3; in the nonventilated room and 61 µ g/m&sup 3; in the ventilated room, and were substantially higher than concentrations in the sitting adult breathing zone. Concentrations of approximately 30 µ g/m&sup 3; were detected in the infant breathing zone 24 hours post-application. Surface residues available through wipe sampling were 0.7-1.6 µ g/cm&sup 2; of carpet on the day of application and 0.3-0.5 µ g/cm&sup 2; 24 hours post-application. Estimated total absorbed doses for infants were 0.08-0.16 mg/kg on the day of application and 0.04--0.06 mg/kg the day following application, with dermal absorption representing approximately 68 percent of the totals. These doses are 1.2-5.2 times the human No Observable Effect Level (NOEL). Exposures to cholinesterase inhibiting compounds following properly conducted broadcast applications could result in doses at or above the threshold of toxicological response in infants, and should be minimized through appropriate regulatory policy and public education. (Am J Public Health 1990; 80:689-693.) [ABSTRACT FROM AUTHOR]

Barnacles are ubiquitous in coastal ecosystems of different geographical regions worldwide. This is the first study attempting to assess the suitability of barnacles as bioindicators of persistent organic pollutants (POPs) in coastal environments. Barnacles were collected from the coasts around Peninsular Malaysia and analyzed for POPs including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs). Among POPs, PCBs showed the highest concentrations with elevated contributions of CB28 and CB153. As for PBDEs, BDE47 was the most frequently detected congener, while BDE209 was detected in barnacles from two stations in Port Klang and the levels reached up to >70% of total PBDE concentrations. Concentrations of OCPs detected in barnacles were in the order of CHLs > DDTs > HCHs > HCB and 4,4′-DDE and cis - and trans -chlordane were the predominant OCP compounds. A comparison with previous studies in Malaysia showed consistent levels of POPs. Green mussels collected from selected barnacles' habitats, for the sake of a comparison, showed almost similar profiles but lower concentrations of POPs. The spatial distribution of POPs observed in barnacles and comparison of POP levels and profiles with mussels indicated that barnacles can be useful bioindicators for monitoring POPs contamination in the coastal ecosystems. Image 1 • Coastal biomonitoring survey on POPs was conducted using barnacles from Malaysia. • Elevated levels of PCBs and PBDEs were found in barnacles from a populated area. • Compositions of CHLs, DDTs and HCHs indicated their recent use. • Almost similar profiles of POPs were observed between barnacles and mussels. • Barnacles can be useful bioindicators of POPs in coastal ecosystems worldwide. [ABSTRACT FROM AUTHOR]

A correction to the article "Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases," by E. A. Moehle, J. M. Rock, Y. L. Lee, Y. Jouvenot, R. C. DeKelver, P. D. Gregory, F. D. Urnov, and M. C. Holmes that was published in the February 27, 2007 issue is presented.

A large-area and periodically patterned nanoporous aluminum grid with controlled pore size was fabricated by poly(ethylene oxide)-assisted self-assembly of polystyrene nanospheres. The grid layer was used as the shadow mask for the creation of nanochannels in a polymeric dielectric layer, as well as the base electrode in a space-charge limited transistor prepared thereafter. A high performance device with poly(3-hexylthiophene) as conducting semiconductor was achieved, yielding a high on-current output of ∼12 mA/cm2 and a high on-off ratio of ∼2 × 104 at a collector voltage of -2.0 V. [ABSTRACT FROM AUTHOR]

We have developed an approach to prepare large array nanostructured thin films using polyethylene oxide assisted self-assembly of polystyrene nanospheres as a template. By tuning the antidot diameter in the cobalt thin films, we found a crossover behavior in the magnetization reversal process. In addition, the effective moment per cobalt atom turns out to drop with growing antidot diameter which effectively increases the surface to bulk volume fraction. Our results suggest a tendency of reduced saturation magnetization in a ferromagnet/normal metal interface, where the mixing of itinerant electrons with ferromagnetic d electrons can give rise to observable effect. [ABSTRACT FROM AUTHOR]

In this study, glass fiber (GF)/phenol formaldehyde resin (PF)/epoxy resin (EP) three-phase electrical insulating composites were fabricated by selective laser sintering (SLS) additive manufacturing technology and subsequent infiltration. In the three-phase composites, glass fibers modified by a silane coupling agent (KH-550) were used as reinforcements, phenol formaldehyde resin acted as the binder and matrix, and infiltrated epoxy resin was the filler. Mechanical and electrical properties such as tensile strength, bending strength, dielectric constant, electrical conductivity, and electric breakdown strength of the GF/PF/EP three-phase composite parts were investigated. The results indicated that after being infiltrated with EP, the bending strength and tensile strength of the GF/PF/EP composites increased by 30% and 42.8%, respectively. Moreover, the flexural strength and tensile strength of the GF/PF/EP composite increased with the increase of the glass fiber content. More importantly, the three-phase composites showed high electrical properties. Significant improvement in the dielectric constant, electric breakdown strength, and resistivity with the increase in the content of glass fiber was observed. This enables the prepared GF/PF/EP composites to form complex structural electrical insulation devices by SLS, which expands the materials and applications of additive manufacturing technology. [ABSTRACT FROM AUTHOR]

Dirac nodal line semimetals represent a new state of quantum matters in which the electronic bands touch to form a closed loop with linear dispersion. Here, we report a combined study on ZrSiS by density functional theory calculation, scanning tunnelling microscope (STM) and magneto-transport measurements. Our STM measurements reveal the spectroscopic signatures of a diamond-shaped Dirac bulk band and a surface band on two types of cleaved surfaces as well as a spin-polarized surface band at at E ∼ 0.6 eV on S-surface, consistent with our band calculation. Furthermore, we find the surface termination does not affect the surface spectral weight from the Dirac bulk bands but greatly affect the surface bands due to the change in the surface orbital composition. From our magneto-transport measurements, the primary Shubnikov–de-Haas frequency is identified to stem from the hole-type quasi-two-dimensional Fermi surface between Γ and X. The extracted non-orbital magnetoresistance (MR) contribution D(θ, H) yields a nearly H-linear dependence, which is attributed to the intrinsic MR in ZrSiS. Our results demonstrate the unique Dirac line nodes phase and the dominating role of Zr-d orbital on the electronic structure in ZrSiS and the related compounds. [ABSTRACT FROM AUTHOR]

In a superconducting nanostructure, phase fluctuations are prominent and give rise to finite resistance below superconducting transition temperature Tc. By using a monolayer polymer/nanosphere hybrid we developed previously, we fabricated a large array of interconnected niobium (Nb) honeycomb lattices with the thinnest interconnected linewidth d ranging from 36 nm to 89 nm. The honeycomb cells form a highly ordered triangular lattice with more than 108 unit cells extending over few mm² area, which enables the detailed transport study at nanometer scales. We found Tc gradually drops with decreasing d due to the phase-slip effect, while the critical field at lower temperature tends to follow that of a continuous Nb thin film. One likely scenario is to consider a model system of numerous superconducting islands interconnected by short phase-slip junctions, where the phase coherence is dictated by the phase slippage in the nanoconstriction. This was strongly supported by the excellent fitting to the thermally activated phase-slip model and also the unusual phenomena of transition width narrowing in high fields. [ABSTRACT FROM AUTHOR]

Low-dimensional materials could display anomalous thermal conduction that the thermal conductivity (κ) diverges with increasing lengths, in ways inconceivable in any bulk materials. However, previous theoretical or experimental investigations were plagued with many finite-size effects, rendering the results either indirect or inconclusive. Indeed, investigations on the anomalous thermal conduction must demand the sample length to be sufficiently long so that the phenomena could emerge from unwanted finite-size effects. Here we report experimental observations that the κ's of single-wall carbon nanotubes continuously increase with their lengths over 1 mm, reaching at least 8640 W/mK at room temperature. Remarkably, the anomalous thermal conduction persists even with the presence of defects, isotopic disorders, impurities, and surface absorbates. Thus, we demonstrate that the anomalous thermal conduction in real materials can persist over much longer distances than previously thought. The finding would open new regimes for wave engineering of heat as well as manipulating phonons at macroscopic scales. [ABSTRACT FROM AUTHOR]

Twenty-four patients were treated with escalating doses from one to sixty milligrams (mg) of SB-509, a plasmid DNA expressing a zinc finger transcription factor for VEGF, in a Phase 1a/b clinical trial. Treatment Plan 1 consisted of administration of SB-509 in one leg and placebo in the contralateral leg at dose levels of 1, 5, 10, 15 and 30 mg. Treatment Plan 2 consisted of administration in both legs with either SB-509 or placebo at dose levels of 30 mg and 60 mg. Three placebo patients and three SB-509 patients were treated at each dose level in Treatment Plan 2. Patients were evaluated using the Total Neuropathy Score (TNS), a composite scale incorporating symptoms, neurologic exam, and nerve testing, nerve conduction velocities (NCV), and quantitative sensory testing (QST). A statistically significant improvement in motor NCVs was seen at dose level 6 (60mg) at the six-month time-point when comparing the sum of all motor NCV (2 peroneal and 2 tibial NCV per patient) improvements from baseline to placebo. The mean value of improvement in the SB509 group (three patients) was 3.934 M/Sec compared to -0.52 M/see in the placebo group (six patients) (p < 0.0383). QST testing at six months showed a 43% improvement in vibration units from baseline at dose level 6 in the SB509 group compared to 20% worsening in the placebo group (p< 0.0058). The TNS at six months showed improvement in this scale with a mean score of 1.675 in the SB-509 group compared to a mean improvement 0f0.665 in the placebo group at dose level 6. Improvements in NCV included three patients with unmeasurable NCVs who, after treatment with SB-509, NCV returned and improved over the six-month follow-up. The dose level of 60 mg showed consistent improvements in the neurologic exam, QST and motor NCV. These improvements in neurologic endpoints suggest that SB-509 has novel regenerative potential for the reversal of nerve damage in Diabetic Neuropathy. The 60 mg dose level has been expanded to accrue a total of 24 patients to further evaluate the long term effects of a single treatment of SB-509 and a Phase 2 trial in mild to moderate diabetic neuropathy has been initiated. [ABSTRACT FROM AUTHOR]

We have shown previously that human genome editing can be performed at high efficiency using designed zinc finger nucleases (ZFNs). ZFNs can be engineered to generate a double-strand break at a specific chromosomal location both in transformed and primary human cells. These breaks are repaired by the cell's own DNA repair machinery, and when a homologous extrachromosomal donor molecule is provided, a homology-directed repair process leads to highly efficient transfer of single-base-pair changes into the chromosome (Urnov et al. Nature 435: 646). ZFNs can be engineered to target virtually any chromosomal location (Pabo et al., Ann. Rev. Biochem. 70: 313), and function robustly in human hematopoietic stem cells, hence such localized gene modification may potentially be useful in the correction and treatment of certain monogenic diseases. Here we show that ZFNs can also be used for the preciseinsertion of a novel sequence into a pre-determined location in the human genome. Remarkably, this novel sequence can constitute a short patch sequence or several kilobases of one or more transgenes. We have observed ZFN-driven targeted integration into endogenous chromosomal loci in human cells of entire open reading frames and promoter-transcription units at a frequency of 5% in the absence of any selection. We also show the use of this process to disrupt with high efficiency an endogenous chromosomal locus with a selectable marker ORF. Finally, we describe our work on using ZFN-driven integration to insert a therapeutically-relevant transgene into a “safe-harbor” locus in the human genome, potentially avoiding the problem of insertional mutagenesis. Hence, the homology-directed repair process invoked by the ZFNs can be used to carry out high-efficiency targeted integration to potentially improve the safety and efficacy of gene therapy.Molecular Therapy (2006) 13, S386–S387; doi: 10.1016/j.ymthe.2006.08.1097 [ABSTRACT FROM AUTHOR]

HIV entry into target cells requires binding of the envelope protein GP120 to the CD4 co-receptors CCR5 or CXCR4. Loss of these HIV co-receptors is therefore attractive as a potential therapy for HIV patients, yet no current methods permit the efficient therapeutic disruption of a chosen gene in the human genome. To this end, we have developed designed zinc-finger protein nucleases (ZFNs) to target predetermined sequences within the CCR5 gene. Once these ZFNs create a double strand break (DSB) in the targeted DNA, natural DNA repair pathways, including Non-Homologous End Joining (NHEJ), subsequently repair the DSB. Importantly, however, NHEJ is error prone and thus can result in permanent disruption of the targeted gene.Designed ZFNs that recognize coding sequences within the CCR5 gene were generated and their DNA-binding and cleavage properties were determined in vitro. Vectors encoding the validated ZFNs were introduced into human cells for in vivo assessment of function. ZFNs targeted to the CCR5 co-receptor efficiently cleaved their expected DNA target sites, leading to high efficiency target gene disruption (>5%) in transiently transfected cells even in the absence of selective pressure. These results have been confirmed in relevant primary cell types (monocytes, CD4+ T cells, CD34+ hematopoietic precursors). We also demonstrated that PM-1 and GHOST cells modified by the CCR5-ZFNs became resistant to HIV infection. Challenge assays using T cells pre-treated with these ZFNs are in progress, although it is well established that a patients cells carrying a deletion within the CCR5 gene are resistant to infection despite repeated exposure to R5-tropic virus. Moreover, the frequency of gene disruption observed supports its examination as a possible method for the therapeutic modification of isolated patient cells to generate HIV resistant T cells or hematopoietic precursors.Molecular Therapy (2006) 13, S293–S293; doi: 10.1016/j.ymthe.2006.08.842 [ABSTRACT FROM AUTHOR]

Zinc finger nucleases have been shown to be effective tools for high-frequency genome editing with potential therapeutic applications (Urnov et al., Nature 435:646-651). Such nucleases are created by fusing the cleavage domain of the type IIs restriction enzyme Fok I to engineered zinc finger proteins. One limitation of this architecture is that the natural Fok I cleavage domain must dimerize in order to cleave DNA; therefore two different zinc finger protein-Fok I fusions are required to introduce a double-stranded break at an asymmetric target site. As a consequence, use of this technology for genome editing may expose the cell to three different nuclease species – the desired heterodimer as well as two homodimers which are irrelevant to the desired process but which may still contribute to off-target cleavage events.Creating Fok I cleavage domain variants that do not function as homodimers would eliminate the possibility of off-target cutting by these species and would also increase the availability of the desired heterodimer. In order to develop such variants, we used a process of iterative structure-based design and screening in which candidate designs were tested for their ability to cleave DNA in vitro and for their ability to potentiate gene correction in a reporter cell line. A pair of nuclease variants, each containing two mutations at the dimerization interface, were developed that worked well when paired together, but were severely impaired when paired with a second copy of themselves. These mutant cleavage domains were substituted for the wild-type FokI cleavage domains in the reagents used by Urnov et al. and tested for their ability to induce sequence alterations at the endogenous human common gamma chain gene. In this system we observed that a heterodimer of our designed cleavage domains was as active as wild type Fok I at stimulating gene correction while inducing significantly fewer overall DNA cutting events. Moreover, homodimers of the designed Fok I cleavage domain variants were completely inactive. These studies demonstrate that we have successfully developed Fok I cleavage domain variants that function as obligate heterodimers. These variants should be broadly useful for increasing the potency and specificity of designed zinc finger nucleases.Molecular Therapy (2006) 13, S305–S305; doi: 10.1016/j.ymthe.2006.08.875 [ABSTRACT FROM AUTHOR]