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We present a quantitative sandwich immunoassay for CD63 Extracellular Vesicles (EVs) and a constituent surface cargo, EGFR and its activity state, that provides a sensitive, selective, fluorophore-free and rapid alternative to current EV-based diagnostic methods. Our sensing design utilizes a charge-gating strategy, with a hydrophilic anion exchange membrane functionalized with capture antibodies and a charged silica nanoparticle reporter functionalized with detection antibodies. With sensitivity and robustness enhancement by the ion-depletion action of the membrane, this hydrophilic design with charged reporters minimizes interference from dispersed proteins, thus enabling direct plasma analysis without the need for EV isolation or sensor blocking. With a LOD of 30 EVs/μL and a high relative sensitivity of 0.01% for targeted proteomic subfractions, our assay enables accurate quantification of the EV marker, CD63, with colocalized EGFR by an operator/sample insensitive universal normalized calibration. We analysed untreated clinical samples of Glioblastoma to demonstrate this new platform. Notably, we target both total and "active" EGFR on EVs; with a monoclonal antibody mAb806 that recognizes a normally hidden epitope on overexpressed or mutant variant III EGFR. Analysis of samples yielded an area-under-the-curve (AUC) value of 0.99 and a low p-value of 0.000033, surpassing the performance of existing assays and markers. Targeting conformally-active EGFR on small extracellular vesicles using a novel Charge-gated Ion Exchange Membrane sensor allows sensitive and non-invasive detection of Glioblastoma in human subjects from untreated plasma. [ABSTRACT FROM AUTHOR]

A flexible wearable electrode consisting of nickel–cobalt sulfide (NCS) nanowires was fabricated in this study. Self-supporting NCS was grown in situ on porous carbon nanofibers without a binder as a novel material for supercapacitor electrodes. The NCS nanowires were grown using cyclic voltammetry electrodeposition, which proved to be a fast and environmentally friendly method with good controllability of the material structure. One-dimensional carbon nanofibers (C) have high surface-area-to-volume ratios, short ion transmission distances, excellent mechanical strengths, and remarkable flexibilities. Moreover, the NCS@C flexible electrode exhibited a synergetic effect with the active compounds, and the dense active sites were uniformly distributed across the entire surface of the carbon fibers, enabling rapid electron transport and enhancing the electrochemical properties of the NCS@C nanowires. The NCS@C achieved specific capacitances of 334.7 and 242.0 mAh g−1 at a current density of 2 A g−1 and high current densities (up to 40 A g−1), respectively, corresponding to a 72.3% retention rate. An NCS@C-nanofilm-based cathode and an activated-carbon-based anode were used to fabricate a flexible asymmetric supercapacitor. The device exhibited high energy and power densities of 12.91 Wh kg−1 and 358 W kg−1, respectively. [ABSTRACT FROM AUTHOR]

Purpose: The O-(2-[18F]-fluoroethyl)-l-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. Methods: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). Results: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00–30.10%), 5.89% (5.01–6.68%), and 5.01% (3.37–6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63–0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. Conclusion: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed. [ABSTRACT FROM AUTHOR]

Purpose: This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free survival (PFS), adverse effects (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG). Methods: A search was performed on PubMed, Scopus, Embase and CENTRAL. Studies reporting OS, PFS, AEs and/or QoL and encompassing the following groups were included; reirradiation vs systemic therapy, combination therapy vs systemic therapy, combination therapy vs reRT, and bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy. Meta-analyses were performed utilising a random effects model. Certainty of evidence was assessed using GRADE. Results: Thirty-one studies (three randomised, twenty-eight non-randomised) comprising 2084 participants were included. In the combination therapy vs systemic therapy group, combination therapy improved PFS (HR 0.57 (95% CI 0.41–0.79); low certainty) and OS (HR 0.73 (95% CI 0.56–0.95); low certainty) and there was no difference in grade 3 + AEs (RR 1.03 (95% CI 0.57–1.86); very low certainty). In the combination therapy vs reRT group, combination therapy improved PFS (HR 0.52 (95% CI 0.38–0.72); low certainty) and OS (HR 0.69 (95% CI 0.52–0.93); low certainty). In the bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy group, adding bevacizumab improved PFS (HR 0.46 (95% CI 0.27–0.77); low certainty) and OS (HR 0.42 (95% CI 0.24–0.72; low certainty) and reduced radionecrosis (RR 0.17 (95% CI 0.06–0.48); low certainty). Conclusions: Combination therapy may improve OS and PFS with acceptable toxicities in patients with rHGG compared to reRT or systemic therapy alone. Particularly, combining bevacizumab with reRT prophylactically reduces radionecrosis. Registration: CRD42022291741. [ABSTRACT FROM AUTHOR]

Abstract Conduct disorders (CDs) are common in juvenile justice cases, but their prevalence varies across regions. It is useful to help people comprehend the incidence and risk factors for CDs in the judicial environment. To determine the prevalence of CDs among juvenile delinquents in China and explore the risk factors for CDs in terms of demographic characteristics, individual characteristics, and social environmental factors. A total of 545 male juvenile delinquents and 297 typically developed adolescents from China were recruited for this study. The Conduct Disorder Screening Form was used to assess the symptoms of CD, and related measurements, including the Demographic Questionnaire, Short-Egna Minnen av Barndoms Uppfostran for Chinese (s-EMBU-C), the Short Form of the Childhood Trauma Questionnaire (CTQ-SF), the Parental Monitoring Scale, the Deviant Peer Affiliation Scale, the Inventory of Callous-Unemotional Traits (ICU), the Self-Control Scale (SCS), and the Moral Disengagement Scale (MDS), were carried out. Among the juvenile delinquents, 58.7% met the symptoms of CD, with adolescent-onset CD accounting for 90.94% of these cases. There was no statistically significant difference in the incidence of CD between the criminal group and the illegal group, but the criminal group scored higher on aggression than the illegal group. The adolescents with CDs differed from the typically developed adolescents in demographic characteristics, parenting style, individual characteristics, and deviant peer affiliation. Discriminant analysis revealed that deviant peer affiliation had the greatest impact on the CDs of adolescents (structural matrix = 0.85), followed by the level of parental monitoring and moral disengagement. CD is widespread in Chinese juvenile delinquents. CD symptoms differ between criminal and illegal juvenile delinquents. Risk factors such as deviant peer affiliation, inadequate parental monitoring, moral disengagement, and low parental warmth all contribute to the high prevalence of CD.

Ephrin type-A 2 (EphA2) is a transmembrane receptor expressed in epithelial cancers. We report on a phase I dose escalation and biodistribution study of DS-8895a, an anti-EphA2 antibody, in patients with advanced EphA2 positive cancers. DS-8895a was administered at 1, 3, 10 or 20 mg/kg every 2 weeks to determine safety, pharmacokinetics and anti-tumor efficacy. All patients underwent 89Zr trace-labelled infusion of DS-8895a (89Zr-DS-8995a) positron emission tomography imaging to determine the biodistribution of DS-8895a, and correlate findings with EphA2 expression, receptor saturation and response. Nine patients were enrolled on study. Of patients enrolled, seven patients received at least one infusion of DS-8895a: four patients received 1 mg/kg dose (Cohort 1) and three patients received 3 mg/kg dose (Cohort 2). Median age was 67.0 years (range 52—81), majority male (71%), and median number of prior systemic therapies was three (range 0—8). The primary cancer diagnosis was colorectal cancer (two patients) and one patient each had gastric, head and neck, high-grade serous adenocarcinoma, lung, and pancreatic cancers. No dose-limiting toxicities or treatment-related adverse events reported. The best response for the patients in Cohort 1 was stable disease and in Cohort 2 was progressive disease. 89Zr-DS-8895a demonstrated no normal tissue uptake and specific low-grade uptake in most tumours. DS-8895a had limited therapeutic efficacy at doses evaluated and 89Zr-DS-8895a demonstrated low tumour uptake. The biodistribution data from this study were key in halting further development of DS-8895a, highlighting the importance of biodistribution studies in drug development. (Trial registration: ClinicalTrials.gov Identifier NCT02252211). [ABSTRACT FROM AUTHOR]

Background: Pamiparib, a PARP1/2 inhibitor, demonstrated antitumor activity in preclinical models.Methods: This Phase 1A/1B dose-escalation/dose-expansion study enrolled adults (≥18 years) with advanced/metastatic cancer. The dose-escalation phase evaluated the recommended Phase 2 dose (RP2D), maximum tolerated dose (MTD), and pharmacokinetics; the dose-expansion phase evaluated the antitumor activity and food effects.Results: Patients (N = 101) were enrolled in dose-escalation (n = 64) and dose-expansion (n = 37). During BID dose-escalation, dose-limiting toxicities were Grade 2 nausea (n = 1, 40 mg; n = 1, 80 mg); Grade 2 nausea and Grade 2 anorexia (n = 1, 120 mg), Grade 2 nausea, Grade 3 fatigue and Grade 3 paraesthesia (n = 1, 120 mg); MTD was 80 mg BID and RP2D was 60 mg BID. Common adverse events (AEs) were nausea (69.3%), fatigue (48.5%) and anaemia (35.6%); the most common Grade ≥3 AE was anaemia (24.8%). There was a dose-proportional increase in pamiparib exposure; no food effects on pharmacokinetics were observed. In the efficacy-evaluable population (n = 77), objective response rate (ORR) was 27.3% (95% CI, 17.7-38.6%). Median duration of response was 14.9 months (95% CI, 8.7-26.3). In the epithelial ovarian cancer (EOC)-evaluable population (n = 51), ORR was 41.2% (95% CI, 27.6-55.8%).Conclusions: Pamiparib was tolerated with manageable AEs, and antitumor activity was observed in patients with EOC. CLINICALTRIALS.Gov Identifier: NCT02361723. [ABSTRACT FROM AUTHOR]

Introduction: Tumor hypoxia is a centerpiece of disease progression mechanisms such as neoangiogenesis or aggressive hypoxia-resistant malignant cells selection that impacts on radiotherapy strategies. Early identification of regions at risk for recurrence and prognostic-based classification of patients is a necessity to devise tailored therapeutic strategies. We developed an image-based algorithm to spatially map areas of aerobic and anaerobic glycolysis (Glyoxia). Methods: 18F-FDG and 18F-FMISO PET studies were used in the algorithm to produce DICOM-co-registered representations and maximum intensity projections combined with quantitative analysis of hypoxic volume (HV), hypoxic glycolytic volume (HGV), and anaerobic glycolytic volume (AGV) with CT/MRI co-registration. This was applied to a prospective clinical trial of 10 glioblastoma patients with post-operative, pre-radiotherapy, and early post-radiotherapy 18F-FDG and 18F-FMISO PET and MRI studies. Results: In the 10 glioblastoma patients (5M:5F; age range 51–69 years), 14/18 18F-FMISO PET studies showed detectable hypoxia. Seven patients survived to complete post-radiotherapy studies. The patient with the longest overall survival showed non-detectable hypoxia in both pre-radiotherapy and post-radiotherapy 18F-FMISO PET. The three patients with increased HV, HGV, and AGV volumes after radiotherapy showed 2.8 months mean progression-free interval vs. 5.9 months for the other 4 patients. These parameters correlated at that time point with progression-free interval. Parameters combining hypoxia and glycolytic information (i.e., HGV and AGV) showed more prominent variation than hypoxia-based information alone (HV). Glyoxia-generated images were consistent with disease relapse topology; in particular, one patient had distant relapse anticipated by HV, HGV, and AGV maps. Conclusion: Spatial mapping of aerobic and anaerobic glycolysis allows unique information on tumor metabolism and hypoxia to be evaluated with PET, providing a greater understanding of tumor biology and potential response to therapy. [ABSTRACT FROM AUTHOR]

Composite materials consisting of reduced graphene oxide and LiNiMnO were in situ prepared by a simple one-step hydrothermal treating method. The physical property and electrochemical performance of the composite materials were characterized by X-ray diffraction, Raman spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, cyclic voltammetry, charge/discharge testing, and electrochemical impedance spectroscopy. The results demonstrate that the graphene oxide is partially reduced and uniformly in situ anchored on the surface of LiNiMnO. As a result, the specific surface area of the composite material dramatically increases from 0.2488 to 8.71 m g, and the initial specific discharge capacity improves from 125.8 to 140.2 mAh g, respectively. Furthermore, the capacity retention maintains 95.8% after 100 cycles, and the electrode polarization has significantly been lessened. At rates of 1, 2, and 5 C, the composite material with 5% reduced graphene oxide can deliver much higher capacities than the pristine LiNiMnO. Moreover, AC impedance test results show that the interfacial charge transfer impedance obviously reduced. It is confirmed that the introduction of reduced graphene oxide through hydrothermal treating is effective to enhance the electrochemical performance of the composite material. [ABSTRACT FROM AUTHOR]

Visible light-driven photocatalytic inactivation of Escherichia coli was performed using hydroxyapatite-supported AgPO nanocomposites (AgPO/HA). The antibacterial performance was evaluated by the methods of zone of inhibition plates and minimum inhibitory concentration test. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were employed to investigate the instability and transformation of the nanocomposite by comparing the crystalline, phase, and the morphology before and after exposure to Luria-Bertani culture medium under visible light irradiation. AgPO nanoparticles on the support were found to be shortly transformed into AgCl due to high chloride concentration of Luria-Bertani culture medium. The AgCl/HA nanocomposite showed both excellent intrinsic antibacterial performance contributed by the released silver ions and visible light-induced photocatalytic disinfection toward E. coli cells. This dual antibacterial function mechanism was validated by trapping the hydroxyl free radical and detecting the silver ions during the photocatalytic antibacterial process. The morphological change of E. coli cells in different reaction intervals was obtained by scanning electron microscopy (SEM) to complementally verify photocatalytic inactivation of E. coli. This work suggests that an essential comparison study is required for the antibacterial materials before and after the photocatalytic inactivation of bacterial cells using AgPO nanoparticles or AgPO-related nanocomposites in mediums containing high-concentration chloride ions. [ABSTRACT FROM AUTHOR]

A green emitting BaSiON:Eu phosphor with an appreciable intensity was synthesized using the gas-reduction-nitridation (GRN) method. SEM revealed agglomerated BaSiON:Eu particles with irregular morphologies and a primary particle size of 1-2.5 μm. The phosphor showed emission lines of Eu corresponding to the 4f5d → 4f transition under 370 nm excitation. As the GRN process was conducted to incorporate N into the lattice, both the excitation and emission intensity of BaSiON:Eu were enhanced greatly compared to BaSiO:Eu. The decay time of BaSiON:Eu showed that N entered the BaSiO:Eu lattices to replace O to form a N point defect. The electroluminescence intensity of BaSiON:Eu at 503 nm increased with increasing forward bias current. Intense green LEDs were fabricated by coating the synthesized phosphors on the cap of the near-ultraviolet InGaN LEDs (λ = 375 nm). Overall, this phosphor appears to be a promising candidate for solid-state lighting applications. [ABSTRACT FROM AUTHOR]

This study examined the influence of the Sn doping concentration on the structural, electrical and optical properties of Sn-doped copper oxide (Sn:CuO) thin films synthesized on glass substrates using a facile sol-gel method. The samples were characterized by X-ray diffraction, energy dispersive X-ray analysis, scanning electron microscopy, Hall Effect measurements, and UV-visible spectroscopy. The carrier concentration, Hall mobility and resistivity of the Sn:CuO films were 9.14 × 10-1.08 × 10 cm, 6.14-10.5 cm/Vs and 47.4-77.5 Ω cm, respectively. The crystallite size of the films decreased with increasing Sn content from 84.1 to 61.8 nm. The band gap trended downward from 2.0 to 1.95 eV with increasing Sn doping content. The results showed that SnO doping strongly affects the structural, electrical and optical properties of the films. [ABSTRACT FROM AUTHOR]

Eu-doped red-emitting BaGdBO phosphors were synthesized via a sol-gel process and the conventional solid state method. No concentration quenching of Eu was observed in this research work. The effect of Ca and Sr on the luminescence of BaEuBO (BEB) phosphor was also investigated. The partial replacement of Ba by Sr could improve the luminescence intensity of BEB phosphor remarkably. The luminescent intensity of sol-gel derived is comparable with the solid state product and it is about 92 % of solid-state product prepared at 950 °C under 395 nm light excitation. The emission intensity of the sol-gel derived phosphor is about 10 times higher than that of YEuOS at 395 nm light excitation. Compared with the molybdate based recently reported red-emitting phosphors, the emission intensity of our obtained novel phosphors synthesized by various methods are much stronger under 395 nm excitation. Due to high emission intensity and good excitation profile, these phosphors can be used as red-emitting phosphor in solid-state lighting to generate white light. [ABSTRACT FROM AUTHOR]

Cu-Ni co-doped ZnAlO (AZO; Al/Zn = 1.5 at.%) films with fixed Ni concentration at 0.5 mol% and different Cu concentrations (0-2.0 % mole ratio) were synthesized on glass substrates using a sol-gel method. The effects of the Cu composition on the structure, electrical and optical properties were examined. X-ray diffraction (XRD) of the Cu-Ni co-doped AZO (CuNi:AZO) films revealed a polycrystalline ZnO phase with a hexagonal wurtzite structure. The stress variation of the CuNi:AZO films were analyzed from the XRD pattern. XPS spectra indicated the existence of two valence states of Cu atoms in Cu and Cu states after N/H (95/5) forming gas heat treatment for CuNi:AZO films. Scanning electron microscopy showed that all the films were smooth with a good packing density. The particle size was calculated by both XRD and SEM analysis, and the difference between them has been discussed in detail. Hall measurements indicated that the lowest resistivity of the CuNi:AZO film is approximately 1.16 × 10 Ω cm at a 1.0 mol% Cu content, which is one order of magnitude lower than that of AZO film (1.01 × 10 Ω cm) and 43.9 % lower than that of Ni-doped AZO film (2.07 × 10 Ω cm). All the films exhibited high transmittance in the visible region and showed sharp absorption edges in the UV region. The optical band gap shifted from 3.44 to 3.35 eV with increasing Cu content. This study provides a simple and efficient route for preparing low resistivity and high transparency CuNi:AZO films for optoelectronic applications. [ABSTRACT FROM AUTHOR]

Magnetic nickel ferrite (NiFeO) was prepared by sol-gel process and calcined in the 2.45 GHz singlemode microwave furnace to synthesize nickel nanopowder. The sol-gel method was used for the processing of the NiFeO powder because of its potential for making fine, pure and homogeneous powders. Sol-gel is a chemical method that has the possibility of synthesizing a reproducible material. Microwave energy is used for the calcining of this powder and the sintering of the NiFeO samples. Its use for calcination has the advantage of reducing the total processing time and the soak temperature. In addition to the above combination of sol-gel and microwave processing yields to nanoscale particles and a more uniform distribution of their sizes. X-ray diffraction, energy dispersive X-ray spectroscopy, transmission electron microscopy and vibrating sample magnetometer were carried out to investigate structural, elemental, morphological and magnetic aspects of NiFeO. The results showed that the mean size and the saturation magnetization of the NiFeO nanoparticles are about 30 nm and 55.27 emu/g, respectively. This method could be used as an alternative to other chemical methods in order to obtain NiFeO nanoparticles. [ABSTRACT FROM AUTHOR]

Conventional methods for the preparation and stabilization of amorphous nanoscale zero-valent iron (NZVI) particles are complicated and costly. In this study, a facile and economic approach for synthesizing stable NZVI without the requirement of vacuum condition was explored. NZVI particles were simultaneously prepared and stabilized in non-deoxygenated aqueous solutions. Scanning electron microscopy, energy dispersive xray microanalysis (EDX), and x-ray photoelectron spectroscopy results showed that the as-prepared Fe were uniform spherical particles with a diameter ranging from 50 nm to 100 nm and a ∼5 nm thick oxide shell. The x-ray diffraction (XRD) patterns indicated that the main component of the particles was amorphous Fe. As confirmed via EDX and XRD analyses, the Fe content in the stabilized NZVI particles was hardly changed after six months of storage in dry atmosphere. [ABSTRACT FROM AUTHOR]

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn's disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2, in which three causal, uncommon and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with P-value <10−3, respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare CD-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association. [ABSTRACT FROM AUTHOR]

We provide an overview of the latest developments in cancer gene therapy-from the bench to early-stage clinical trials. We describe the most recent work of worldwide teams including experienced scientists and clinicians, reflecting the recent emergence of gene therapy from the 'Valley of Death'. The treatment efficacy of clinical gene therapy has now been shown in a number of diseases including cancer and we are observing a renewed interest by big pharmaceutical and biotechnology companies most obviously demonstrated by Amgen's acquisition of Biovex for up to USD$1 billion. There is an opportunity to be cautiously hopeful regarding the future of gene therapy in the clinic and we review here some of the most recent progress in the field. [ABSTRACT FROM AUTHOR]

In this work, nickel cobaltite (NiCo2O4) nanosheets with a porous structure were fabricated on nickel foam as a working electrode for supercapacitor applications. The nanosheets were fabricated by electrochemical deposition of nickel–cobalt hydroxide on the nickel foam substrate at ambient temperature in a three-electrode cell followed by annealing at 300 °C to transform the coating into a porous NiCo2O4 nanosheet. Field emission scanning electron microscopy and transmission electron microscopy revealed a three-dimensional mesoporous structure, which facilitates ion transport and electronic conduction for fast redox reactions. For one cycle, the NiCo2O4 electrodeposited nickel foam has a high specific capacitance (1734.9 F g−1) at a current density (CD) of 2 A g−1. The electrode capacitance decreased by only approximately 12.7% after 3500 cycles at a CD of 30 A g−1. Moreover, a solid-state asymmetric supercapacitor (ASC) was built utilising the NiCo2O4 nanosheets, carbon nanotubes, and a polyvinyl alcohol-potassium hydroxide gel as the anode, cathode, and solid-state electrolyte, respectively. The ASC displayed great electrochemical properties with a 42.25 W h kg−1 energy density at a power density of 298.79 W kg−1. [ABSTRACT FROM AUTHOR]

One of the major challenges in cancer gene therapy is the identification of functionally relevant tumor-specific genes as the therapeutic targets. MicroRNAs (miRNAs) are a class of small, 22-25 nucleotides, endogenously expressed noncoding RNA. miRNAs are important genetic regulators: one miRNA can possibly target multiple genes and they can function as tumor promoters (oncogenic miRNAs, oncomirs) or tumor suppressors (anti-oncomirs). Therefore, the identification of misregulated miRNAs in cellular signaling pathways related to oncogenesis can have profound implications for cancer therapy. The epithelial-mesenchymal transition (EMT) converts epithelial cells into mesenchymal cells, a normal embryological process that frequently get activated during cancer invasion and metastasis. Recent evidence also supports the presence of a small subset of self-renewing, stem-like cells within the tumor mass that possess the capacity to seed new tumors and they have been termed 'cancer stem cells (CSC)'. Conceivably, these CSCs could provide a resource for cells that cause therapy resistance. Although the cell origin of CSCs remains to be fully elucidated, a growing body of evidence has demonstrated that the biology of EMT and CSCs is tightly linked with the sequences and compositions of miRNA molecules. Therefore, targeting miRNAs involved in EMT and CSCs regulation can provide novel miRNA-based therapeutic strategies in oncology. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is usually refractory to the available treatments. For cancer gene therapy purposes, real-time imaging of therapeutic gene expression is of great importance because there are multiple factors that modulate the therapeutic gene expression in a complex tumor microenvironment. As a consequence, multiple doses of therapeutic viral vectors may be required for improved efficacy. In the present study, the luciferase reporter gene and the yeast cytosine deaminase (yCD) genes were bicistronically expressed using the foot-and-mouth disease virus 2A peptide under the regulation of the cytomegalovirus (CMV) promoter. The effectiveness of the yCD/5-FC (5-fluorocytosine) killing efficacy mediated by the herpes simplex virus type 1 (HSV-1) amplicon viral vector was shown using HCC and non-HCC cell lines in vitro. In addition, in vivo experiment also showed tumor regression of a primary HCC 26-1004 tumor xenograft in tumor expressing high levels of the yCD gene (as determined by noninvasive imaging) after intratumoral injection of 1.5 × 106 TU HGCX-L2C HSV-1 amplicon viral vector and 5-FC administration. The HSV-1 amplicon viral vector coupled with the yCD/5-FC prodrug activated suicide gene could potentially be of use in clinical gene therapy for HCC. [ABSTRACT FROM AUTHOR]

Surface plasmon tuning via thermally induced refractive index changes in ferroelectrics is investigated. Epitaxial (BaSr)TiO (BST) thin films were deposited on MgO (001) substrates by pulsed laser deposition. The refractive index of BST thin films measured by the prism-coupling technique was found to increase from 2.3932 (TE)/1.9945 (TM) at room temperature to 2.3949 (TE)/1.9965 (TM) at 66°C. Then 30-nm-Ag gratings with periodicity 750 nm and width 300 nm were fabricated on BST by soft ultraviolet nanoimprint lithography and subsequent lift-off process. The reflection spectra from 500 to 1000 nm with incident angle from 5° to 60° were measured at room temperature and 66°C, with a collimated and p-polarized light incident perpendicularly to the grating direction. Several modes were observed from the spectra. At 66°C, a red shift of a dip at about 850 nm by 2 nm was obtained at an incident angle of 15°. Calculations confirmed that the observed modes belong to the (−1), (2), (−2) and (3) surface plasmon modes from the Ag and BST interfaces and localized mode; the red shift by thermal tuning is also confirmed. The results indicate the feasibility of active modulation in surface plasmon resonance in solid-state structures. [ABSTRACT FROM AUTHOR]

Inhibitor of apoptosis protein (IAP)-binding proteins such as Grim, Reaper and HID have been shown to exert a critical role in regulating caspase activity in species such as D. Melanogaster. However, a comparable role for the mammalian homologue of second mitochondrial-derived activator of caspase/direct IAP-binding protein with low pI (Smac/DIABLO) has yet to be clearly established in vivo. Despite tremendous interest in recent years in the use of so-called Smac mimetics to enhance chemotherapeutic potency, our understanding of the true physiologic nature of Smac/DIABLO in regulating programmed cell death (PCD) remains elusive. In order to critically evaluate the role of Smac/DIABLO in regulating mammalian PCD, deficiency of caspase-3 was used as a sensitizing mutation in order to reduce aggregate levels of executioner caspase activity. We observe that combinatorial deletion of Diablo and Casp3, but neither alone, results in perinatal lethality in mice. Consistent with this, examination of both intrinsic and extrinsic forms of PCD in lines of murine embryonic fibroblasts demonstrate that loss of Smac/DIABLO alters both caspase-dependent and caspase-independent intrinsic PCD. Comparative small interfering RNA inhibition studies of X-linked inhibitor of apoptosis, cellular inhibitor of apoptosis (cIAP)-1, cIAP-2, caspase-6 and -7 in both wild-type and Casp3/Diablo DKO mouse embryonic fibroblast lineages, supports a model in which Smac/DIABLO acts to enhance the early phase executioner caspase activity through the modulation of inhibitory interactions between specific IAP family members and executioner caspases-3 and -7. [ABSTRACT FROM AUTHOR]

Vascular invasion is one of the clinicopathologic features that are associated with early recurrence of human hepatocellular carcinoma (HCC). In this study, we have employed high-density Affymetrix oligonucleotide GeneChips (Affymetrix, Santa Clara, CA) to compare the expression profiles of HCC with and without vascular invasion. Data mining of the gene expression database established revealed that leukocyte cell-derived chemotaxin-2 (LECT2) transcripts were downregulated in HCC patients with vascular invasion. Expression of LECT2 in human HCC biopsies was significantly reduced (P<0.0001, fold change=−7.2) when compared with non-tumorous adjacent liver tissues. The reduction of LECT2 expression was significantly correlated with the early recurrent and poor prognosis of the patient (P=0.024). To validate the ability of LECT2 to repress the growth of HCC, an adenoviral vector encoding the secreted human LECT2 (AdLECT2) was introduced into the human HCC cell lines Hep3B and PLC/PRF/5, which do not express endogenous LECT2. Over-expression of LECT2 resulted in the significant inhibition of in vitro migration and invasion of the AdLECT2-transfected HCC cells. Additionally, over-expression of AdLECT2 in subcutaneous Hep3B tumor xenografts in athymic nude mice resulted in significant inhibition of tumor growth (P<0.05). In summary, our data not only demonstrated that LECT2 is a candidate prognostic marker of human HCC, but also that therapeutic strategies targeting LECT2 expression is a promising therapy for human HCC. [ABSTRACT FROM AUTHOR]

Immobilized metal affinity chromatography (IMAC) of proteins containing poly-histidine fusion tags is an efficient research tool for purifying recombinant proteins from crude cellular feedstocks at laboratory scale. Nevertheless, to achieve successful purification of large amounts of the target protein for critical therapeutic applications that demand the precise removal of fusion tags, it is important to also take into consideration issues such as protein quality, efficiency, cost effectiveness, and optimal affinity tag choice and design. Despite the many considerations described in this article, it is expected that enhanced selectivity, the primary consideration in the field of protein separation, will continue to see the use of IMAC in solving new purification challenges. In addition, the platform nature of this technology makes it an ideal choice in purifying proteins with unknown properties. Finally, the unique interaction between immobilized metal ions and poly-histidine fusion tag has enabled new developments in the areas of biosensor, immunoassay, and other analytical technologies. [ABSTRACT FROM AUTHOR]

This paper presents a technique for creating 3D fractal art forms automatically. Using this approach, designers can get access to a large number of 3D art shapes that can be modified interactively. This is based on a modified evolutionary algorithm using Fractal Transform (FT) and Iterated Function System (IFS), which provides tunable geometric parameters. Fitness function for measuring the aesthetics of a fractal shape is formulated based on characteristic parameters in fractal theory, including capacity dimension, correlation dimension, and largest Lyapunov exponent. The productivity of visually appealing fractal can be enhanced by using the proposed technique. Experiments demonstrated the effectiveness of the proposed method, which can be applied to the design of jewelry, light fixture, and decorative patterns. [ABSTRACT FROM AUTHOR]

Hirschsprung’s disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 × 10−6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCR-association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. [ABSTRACT FROM AUTHOR]

Targeting cell infection using herpes simplex virus type 1 (HSV-1) vectors is a complicated issue as the process involves multiple interactions of viral envelope glycoproteins and cellular host surface proteins. In this study, we have inserted a human glioma-specific peptide sequence (denoted as MG11) into a peptide display HSV-1 amplicon vector replacing the heparan sulfate-binding domain of glycoprotein C (gC). The modified MG11:gC envelope recombinant vectors were subsequently packaged into virions in the presence of helper virus deleted for gC. Our results showed that the tropism of these HSV-1 recombinant virions was increased for human glioma cells in culture as compared with wild-type virions. The binding of these recombinant virions could also be blocked effectively by pre-incubating the cells with the glioma-specific peptide, indicating that MG11 peptide and the recombinant virions competed for the same or similar receptor-binding sites on the cell surface of human glioma cells. Furthermore, preferential homing of these virions was shown in xenograft glioma mouse model following intravascular delivery. Taken together, these results validated the hypothesis that HSV-1 binding to cells can be redirected to human gliomas through the incorporation of MG11 peptide sequence to the virions. [ABSTRACT FROM AUTHOR]

Human bone marrow-derived mesenchymal stem cells (BM-hMSCs) are nonhematopoietic stem cells that have the potential to differentiate into adipocytes, osteocytes and chondrocytes. Because of its propensity to migrate to the sites of injury and the ability to expand them rapidly, BM-hMSCs have been exploited as potential gene transfer vehicles to deliver therapeutic genes. Herein, we evaluated the feasibility of employing herpes simplex virus type I (HSV-1) amplicon viral vector as a gene delivery vector to BM-hMSCs. High transduction efficiencies were consistently observed in different isolates of BM-hMSCs following infection with HSV-1 amplicon viral vectors. Furthermore, we demonstrated that transduction with HSV-1 amplicon viral vector did not alter the intrinsic properties of the BM-hMSCs. The morphology and cellular proliferation of the transduced BM-hMSCs were not altered. Chromosomal stability, as confirmed by karyotyping and soft agar colony assays, of the transduced BM-hMSCs was not affected. Similarly, transduction with HSV-1 amplicon viral vectors has no effect on the pluripotent differentiation potential and the tumor tropism of BM-hMSCs. Taken together, these results demonstrated that BM-hMSCs could be transduced efficiently by HSV-1 amplicon viral vector in an ‘inert’ manner and thus enable strategies to express potential therapeutic genes in BM-hMSCs.Cancer Gene Therapy (2008) 15, 553–562; doi:10.1038/cgt.2008.27; published online 6 June 2008 [ABSTRACT FROM AUTHOR]

Background This is a randomized clinical trial (RCT) to investigate the efficacy of a job placement and support program designed for workers with musculoskeletal injuries and having difficulties in resuming the work role. The program was planned to help injured workers to successfully return to work (RTW) by overcoming the difficulties and problems during the process of job seeking and sustaining a job using a case management approach. Methodology A total of 66 injured workers were recruited and randomly assigned into the job placement and support group (PS group) or the self-placement group (SP group). A three-week job placement and support program was given to subjects in the PS group while subjects in the control group (SP group) were only given advice on job placement at a workers’ health center. The PS program was comprised of an individual interview, vocational counseling, job preparation training, and assisted placement using the case management approach. The Chinese Lam Assessment of Stages of Employment Readiness (C-LASER), the Chinese State Trait and Anxiety Inventory (C-STAI), and the SF-36 were the outcome measures for the two groups before and after the training program to observe the changes in subjects’ work readiness status, emotional status and their health related quality of life pre- and post-training program. The rate of return to work was measured for both groups of subjects after the training program. Results The results indicated that the rate of success in RTW (73%) was significantly higher in the job placement (PS) group than that of the self-placement (SP) group (51.6%) with P < 0.05. Significant differences were also found in C-STAI ( P < 0.05), SF-36 ( P < 0.05) and C-LASER scores on action ( P < 0.05) between the two groups. Conclusion The job placement (PS) program appeared to have enhanced the employability of injured workers. Workers who participated in the program also showed higher levels of work readiness and emotional status in coping with their work injuries. [ABSTRACT FROM AUTHOR]

Most human cancers are characterized by genetic aberrations accompanied by altered expression and function of numerous genes. Applying genome-wide, microarray gene expression analysis to identify deregulated genes in different tumour types can provide potential gene candidates as diagnostic and prognostic tools and promising targets for drug development. However, the detection of deregulated genes with low levels of expression remains a major challenge. In this study, we have designed a strategy, termed modified suppression subtractive hybridization (mSSH), to identify genes encoding rare transcripts. The strategy entails incorporating the T7-promoter sequence at the 5′ end of the noncoding cDNA strand during first strand cDNA synthesis to generate unidirectional antisense RNA from the resultant cDNA following conventional SSH. These transcripts are subsequently analysed by Affymetrix oligonucleotide gene arrays. Here, we have used five hepatocellular carcinoma (HCC), five breast carcinoma and four nasopharyngeal carcinoma (NPC) biopsies separately as testers and their corresponding normal biopsies as drivers to enrich for low abundance tumour type-specific transcripts. The total detectable number of probe sets following mSSH was reduced almost 10-fold in comparison to those detected for the same resected tumour tissues without undergoing subtraction, thus yielding a subtraction efficacy of over 90%. Using this experimental approach, we have identified 48 HCC-specific, 45 breast carcinoma-specific, and 83 NPC-specific genes. In addition, 115 genes were upregulated in all the three cancer types. When compared to gene-profiling data obtained without mSSH, the majority of these identified transcripts were of low abundance in the original cancer tissues. mSSH can therefore serve as a comprehensive molecular strategy for pursuing functional genomic studies of human cancers.Oncogene (2008) 27, 4128–4136; doi:10.1038/onc.2008.50; published online 10 March 2008 [ABSTRACT FROM AUTHOR]

Proper development of the nervous system requires that a carefully controlled balance be maintained between both proliferation and neuronal survival. The process of programmed cell death is believed to play a key role in regulating levels of neuronal survival, in large part through the action of antiapoptotic proteins, such as Bcl-2. Consistent with this, Bcl-2 has been shown to be a key regulator of apoptotic signaling in post-mitotic neurons. However, we still know remarkably little regarding the role that Bcl-2 plays in regulating the survival of specific motor neuron populations. In the present study, we have examined somatic motor neurons of the lumbar spinal cord, and branchiomotor neurons of the facial nucleus in bcl-2-null mice to determine the differential dependence among motor neuron populations with respect to Bcl-2-mediated survival. Examination of neuronal and axon number, axonal area, and the distribution of axonal loss in bcl-2-null mice demonstrates that, in contrast to the great majority of alpha motor neurons, gamma motor neurons exhibit a unique dependence upon bcl-2 for survival. These results demonstrate, for the first time, the connection between Bcl-2 expression, motor neuron survival, and the establishment of different motor populations.Cell Death and Differentiation (2008) 15, 691–699; doi:10.1038/sj.cdd.4402294; published online 21 December 2007 [ABSTRACT FROM AUTHOR]

p16INK4A (p16) has been suggested to be an early biomarker for the detection of cervical cancer. However, its functional role in cervical cancer is not well characterized. In this study, we reported the consistent and significant upregulation of p16 in cervical cancer tissues when compared to both matched non-tumourous tissues of the same patient and normal cervical tissues from non-cancer patients. We have employed p16 small interfering RNA (siRNA) to dissect the role of p16 in cervical carcinogenesis. Although the silencing of p16 was accompanied by the upregulation of p53, p21 and RB in the p16 siRNA-transfected cells, no significant effect on cell cycle progression was observed. When the p16 siRNA-silenced cells were subjected to DNA damage stress including ultraviolet-irradiation and cisplatin treatments, a significantly higher percentage of apoptotic cells could be observed in the p16-siRNA silenced cells compared to control siRNA-treated cells. Moreover, induction of apoptosis was associated with the activation of p53 through phosphorylation, and this process, when studied by gene profiling experiments, involved both the intrinsic and extrinsic apoptotic pathways. The observation that silencing of p16 expression augments DNA damage-induced apoptosis in cervical cancer cells offers alternative strategies for anti-cancer therapies for human cervical cancer.Oncogene (2007) 26, 6050–6060; doi:10.1038/sj.onc.1210405; published online 19 March 2007 [ABSTRACT FROM AUTHOR]

We have compared the ability of several nanosized bioceramic particles including negatively charged silica (SiO2), neutrally charged hydroxyapatite (HA) and positively charged zirconia (ZrO2) nanoparticles as non-viral vectors for efficient in vivo gene delivery. A mixture of highly monodispersed aqueous suspension of HA or SiO2 nanoparticles, coated with protamine sulfate (PS), complexed efficiently with plasmid DNA and significantly enhanced transgene expression in vitro. In comparison, ZrO2 nanoparticles gave poor transfection efficiency under similar conditions tested. It was also determined that, under the same conditions, PS-SiO2-DNA, but not PS-HA-DNA-nanoplexes, were able to mediate efficient transgene expression in vitro in the presence of 50% serum. Intraperitoneal injections of PS-SiO2-luciferase DNA nanoplexes targeted the highest level of transgene expression in the spleen of recipient mice that lasted for more than 48 h. Injection of PS-SiO2-pNGVL-hFLex-MUC-1 nanoplexes was able to mediate the production of Flt-3L in the sera of recipient mice. Simultaneously, the production of Flt-3L was accompanied by the stimulation of IL-2 and interferon-γ (IFN-γ). Most importantly, the injection of PS-SiO2-pNGVL-hFLex-MUC-1 nanoplexes could mount potent anti-tumour specific immune responses that led to the subsequent regression of parental tumor cells containing the muc-1 determinant.Gene Therapy (2007) 14, 828–835. doi:10.1038/sj.gt.3302937; published online 8 March 2007 [ABSTRACT FROM AUTHOR]

Purpose: This dose escalation study aimed to determine the recommended doses, toxicity and pharmacokinetics of oxaliplatin and gemcitabine given on days 1 and 8 every 21 days. This schedule may maximize dose intensity of both drugs with acceptable or reduced toxicity. Patient and methods: Eligible patients had solid malignancies, no more than two prior courses of chemotherapy, ECOG performance status 0–2, neurotoxicity ≤ NCI-CTC grade 1 and adequate organ function. Dose escalation commenced at oxaliplatin 40 mg/m2 and gemcitabine 750 mg/m2, both given on days 1 and 8 every 21 days, and reached oxaliplatin 80 mg/m2 and gemcitabine 1,500 mg/m2. The two highest dose levels were each expanded to six patients to gain additional toxicity data. Results: There were no dose limiting toxicities related to treatment and an MTD was not reached. Five patients (24%) had grade 3 neutropenia, without associated infection, and seven patients (33%) had grade 3/4 thrombocytopenia. Neurotoxicity was mild and no worse than grade 1. Two patients with mesothelioma (10%) had partial responses and 11 patients (52%) had disease stabilization. No pharmacokinetic interaction between oxaliplatin and gemcitabine was detected. Dose intensity was maximal at level 4 (oxaliplatin 70 mg/m2 and gemcitabine 1,250 mg/m2). Conclusions: This schedule allows oxaliplatin and gemcitabine to be delivered at the full dose intensity of each drug with excellent tolerability and predictable pharmacokinetics. The recommended doses for phase II studies are oxaliplatin 70 mg/m2 and gemcitabine 1,250 mg/m2 on days 1 and 8 every 21 days. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are professional antigen-presenting cells capable of initiating a potent primary immune response, making them an attractive target for cancer immunotherapy. Flt-3 ligand (Flt-3L) is a haematopoietic growth factor that efficiently induces DC expansion in vivo. To achieve a more efficient and effective method of priming tumour-specific, DC-mediated immune response, we generated a DNA vaccine comprising both human Flt-3L and the tumour antigen, MUC-1 (pNGVL-hFLex-MUC-1). We report that pNGVL-hFLex-MUC-1 is able to induce antigen-specific CTL immunity in vivo, resulting in a potent anti-tumour response, and that the Flt-3L component is essential to the efficacy of the DNA vaccine. Moreover, the route of immunization is critical in determining the type of immune response generated; intramuscular (i.m.) immunization with pNGVL-hFLex-MUC-1 conferred tumour protection in contrast to poor response with hydrodynamic-based intravenous delivery. Post-i.m. immunization, we observed a massive infiltration of mononuclear cells to the injection site, comprised predominantly of CD11c+/CD8α− DC. Therefore, we propose that Flt-3L acts as an adjuvant to recruit DC, thereby priming the anti-tumour response. However, systemic expansion of DC prior to immunization did not enhance the specific cellular response, suggesting that it is in situ recruitment or expansion of DC that is critical for pNGVL-hFLex-MUC-1 potency.Gene Therapy (2006) 13, 245–256. doi:10.1038/sj.gt.3302639; published online 15 September 2005 [ABSTRACT FROM AUTHOR]

We have previously reported the construction of a cell cycle-regulated HSV-1 amplicon vector (denoted as pC8-36) that confers luciferase reporter gene activities dependent on cellular divisions. However, luciferase reporter gene is well known for its relatively high sensitivity, thus, it is crucial to evaluate the therapeutic efficacy of a transcriptional targeted vector. In this report, we have engineered the FasL and FADD genes into pC8-36 and demonstrated their efficacy for the treatment of human gliomas in vitro and in vivo. Using trypan blue dye exclusion and TUNEL assay, FasL expression mediated by pC8-36 was shown to induce a significantly higher percentage of cell death in proliferating cells than those observed in the G1-arrested cells. The observed cell killing effect correlated well with the level of FasL protein expression when analyzed by ELISA assay. Furthermore, the incorporation of both FasL and FADD into pC8-36 resulted in the enhancement of apoptosis in the target glioma cells both in vitro and in vivo. Targeting proliferating tumor cells via the transcriptional control of therapeutic genes could potentially improve the safety and efficacy of cancer gene therapy, and thus would allow the development of strategies for more effective anticancer therapies.Cancer Gene Therapy (2006) 13, 44–52. doi:10.1038/sj.cgt.7700864; published online 22 July 2005 [ABSTRACT FROM AUTHOR]

A major challenge for gene therapy is to be able to deliver efficiently the gene of interest to specific cell types. Here we describe a safe and simple effective naked DNA gene delivery method, via inferior vena cava (IVC) injection, to the recipient's kidneys. It was further demonstrated that gene expression was concentrated in the proximal tubular epithelial cells of the cortico-medullary region of the kidney. Confocal microscopy analyses demonstrated the presence of the exogenous DNA in the renal cell membrane 10?min postgene delivery. However, it was only by 30?min that the presence of the exogenous DNA could be detected in the cell cytoplasm and in the nuclei of the renal cells. Stable expression of theß-galactosidase gene could be detected for up to 35 days and no toxicity or any adverse pathological effect associated with the delivery method could be observed. Importantly, this IVC gene delivery method could promote the targeting of genes to carcinoma established in the kidney of SCID mice. These results provide the first evidence to support that stable gene expression could be achieved in the renal cells of kidney and the established carcinoma in the kidneys following in vivo gene delivery with naked DNA and could therefore provide the potential to design protocols for the gene therapy of the kidney diseases.Gene Therapy (2005) 12, 477-486. doi:10.1038/sj.gt.3302433 Published online 13 January 2005 [ABSTRACT FROM AUTHOR]

Consider a network of unreliable links, modelling for example a communication network. Estimating the reliability of the network-expressed as the probability that certain nodes in the network are connected-is a computationally difficult task. In this paper we study how the Cross-Entropy method can be used to obtain more efficient network reliability estimation procedures. Three techniques of estimation are considered: Crude Monte Carlo and the more sophisticated Permutation Monte Carlo and Merge Process. We show that the Cross-Entropy method yields a speed-up over all three techniques. [ABSTRACT FROM AUTHOR]

To identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer, we employed RT--PCR differential display, reverse Northern and Northern blot analysis to compare the gene expression profiles between squamous cell carcinoma biopsies and adjacent histo-pathological normal epithelium tissues. Twenty-eight cDNA clones were isolated that were demonstrated to be consistently over-expressed in squamous cell cervical cancer biopsies of FIGO stages 1B to 3B. Most importantly, it was observed that, in addition to their over-expression in cancer lesions, some of these genes are upregulated in the presumably histo-pathological normal adjacent tissues. Of particular interest is clone G30CC that has been identified to be the gene that encodes S12 ribosomal protein. When employed for RNA--RNA in situ hybridization experiments, expression of G30CC could be detected in the immature basal epithelial cells of histo-pathological normal tissues collected from cervical cancer patients of early FIGO stages. In comparison, the expression of G30CC was not detected in cervical tissues collected from patients admitted for surgery of non-malignant conditions. These results allow the distinct possibility of employing the ribosomal protein S12 gene as an early molecular diagnostic identifier for the screening of human cervical cancer and a potential target employed for cancer gene therapy trials. [ABSTRACT FROM AUTHOR]

The synthesis of a series of novel cationic lipids through the systematic substitution of cholesterol derivatives that could greatly enhance the delivery and expression of plasmid DNA in vitro and in vivo is described. Two of the newly synthesized lipids, designated as NCC4 and NCC10, were chosen to be studied in detail and gave much higher levels of gene expression than that which could be obtained with some of the conventional cationic polymers and cationic liposomes. In vivo studies with both NCC4 and NCC10 also showed better ability in defivering the reporter gene to the target cells through intrasplenic injection. In addition, by varying the DNA/lipid charge ratios, NCC4 and NCC10 can withstand serum inactivation in vitro. However, this does not correlate with the corresponding increase in the level of gene expression following systemic gene delivery with NCC4 and NCC10 in vivo. [ABSTRACT FROM AUTHOR]