Jacobi-Predictor-Corrector Approach for the Fractional Ordinary Differential Equations

We present a novel numerical method, called {\tt Jacobi-predictor-corrector approach}, for the numerical solution of fractional ordinary differential equations based on the polynomial interpolation and the Gauss-Lobatto quadrature w.r.t. the Jacobi-weight function $\omega(s)=(1-s)^{\alpha-1}(1+s)^0$. This method has the computational cost O(N) and the convergent order $IN$, where $N$ and $IN$ are, respectively, the total computational steps and the number of used interpolating points. The detailed error analysis is performed, and the extensive numerical experiments confirm the theoretical results and show the robustness of this method.Comment: 24 pages, 5 figure

Oncolytic viruses as therapeutic cancer vaccines

Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity. With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF (such as T-VEC and Pexa-Vec) or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy. Coadministration with a HDAC inhibitor inhibits innate immunity transiently to promote infection and spread of OVs, and significantly enhances anti-tumor immunity and improves the therapeutic index. Local administration or OV mediated-expression of ligands for Toll-like receptors can rescue the function of tumor-infiltrating CD8+ T cells inhibited by the immunosuppressive tumor microenvironment and thus enhances the antitumor effect. Combination with cyclophosphamide further induces ICD, depletes Treg, and thus potentiates antitumor immunity. In summary, OVs properly armed or in rational combinations are potent therapeutic cancer vaccines. © 2013 Bartlett et al.; licensee BioMed Central Ltd

Testing and comparing two self-care-related instruments among older Chinese adults

Objectives The study aimed to test and compare the reliability and validity, including sensitivity and specificity of the two self-care-related instruments, the Self-care Ability Scale for the Elderly (SASE), and the Appraisal of Self-care Agency Scale-Revised (ASAS-R), among older adults in the Chinese context. Methods A cross-sectional design was used to conduct this study. The sample consisted of 1152 older adults. Data were collected by a questionnaire including the Chinese version of SASE (SASE-CHI), the Chinese version of ASAS-R (ASAS-R-CHI) and the Exercise of Self-Care Agency scale (ESCA). Homogeneity and stability, content, construct and concurrent validity, and sensitivity and specificity were assessed. Results The Cronbach's alpha (α) of SASE-CHI was 0.89, the item-to-total correlations ranged from r = 0.15 to r = 0.81, and the test-retest correlation coefficient (intra-class correlation coefficient, ICC) was 0.99 (95% CI, 0.99±1.00; P<0.001). The Cronbach's α of ASAS-R-CHI was 0.78, the item-to-total correlations ranged from r = 0.20 to r = 0.65, and the test-retest ICC was 0.95 (95% CI, 0.92±0.96; P<0.001). The content validity index (CVI) of SASE-CHI and ASAS-R-CHI was 0.96 and 0.97, respectively. The findings of exploratory and confirmatory factor analyses (EFA and CFA) confirmed a good construct validity of SASE-CHI and ASAS-R-CHI. The Pearson's rank correlation coefficients, as a measure of concurrent validity, between total score of SASE-CHI and ESCA and ASAS-R-CHI and ESCA were assessed to 0.65 (P<0.001) and 0.62 (P<0.001), respectively. Regarding ESCA as the criterion, the area under the receiver operator characteristic (ROC) curve for the cut-point of SASE-CHI and ASAS-R-CHI were 0.93 (95% CI, 0.91±0.94) and 0.83 (95% CI, 0.80±0.86), respectively. Conclusion There is no significant difference between the two instruments. Each has its own characteristics, but SASE-CHI is more suitable for older adults. The key point is that the users can choose the most appropriate scale according to the specific situation.publishedVersionNivå

Relation for the nonequilibrium population of the interface states: effects on the bias dependence of the ideality factors

By an analysis of the exchange of carriers through a semiconductor junction, a general relationship for the nonequilibrium population of the interface states in Schottky barrier diodes has been derived. Based on this relationship, an analytical expression for the ideality factor valid in the whole range of applied bias has been given. This quantity exhibits two different behaviours depending on the value of the applied bias with respect to a critical voltage. This voltage, which depends on the properties of the interfacial layer, constitutes a new parameter to complete the characterization of these junctions. A simple interpretation of the different behaviours of the ideality factor has been given in terms of the nonequilibrium charging properties of interface states, which in turn explains why apparently different approaches have given rise to similar results. Finally, the relevance of our results has been considered on the determination of the density of interface states from nonideal current-voltage characteristics and in the evaluation of the effects of the interfacial layer thickness in metal-insulator-semiconductor tunnelling diodes

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Genome structure of cotton revealed by a genome-wide SSR genetic map constructed from a BC1 population between gossypium hirsutum and G. barbadense

<p>Abstract</p> <p>Background</p> <p>Cotton, with a large genome, is an important crop throughout the world. A high-density genetic linkage map is the prerequisite for cotton genetics and breeding. A genetic map based on simple polymerase chain reaction markers will be efficient for marker-assisted breeding in cotton, and markers from transcribed sequences have more chance to target genes related to traits. To construct a genome-wide, functional marker-based genetic linkage map in cotton, we isolated and mapped expressed sequence tag-simple sequence repeats (EST-SSRs) from cotton ESTs derived from the A₁, D₅, (AD)₁, and (AD)₂genome.</p> <p>Results</p> <p>A total of 3177 new EST-SSRs developed in our laboratory and other newly released SSRs were used to enrich our interspecific BC₁genetic linkage map. A total of 547 loci and 911 loci were obtained from our EST-SSRs and the newly released SSRs, respectively. The 1458 loci together with our previously published data were used to construct an updated genetic linkage map. The final map included 2316 loci on the 26 cotton chromosomes, 4418.9 cM in total length and 1.91 cM in average distance between adjacent markers. To our knowledge, this map is one of the three most dense linkage maps in cotton. Twenty-one segregation distortion regions (SDRs) were found in this map; three segregation distorted chromosomes, Chr02, Chr16, and Chr18, were identified with 99.9% of distorted markers segregating toward the heterozygous allele. Functional analysis of SSR sequences showed that 1633 loci of this map (70.6%) were transcribed loci and 1332 loci (57.5%) were translated loci.</p> <p>Conclusions</p> <p>This map lays groundwork for further genetic analyses of important quantitative traits, marker-assisted selection, and genome organization architecture in cotton as well as for comparative genomics between cotton and other species. The segregation distorted chromosomes can be a guide to identify segregation distortion loci in cotton. The annotation of SSR sequences identified frequent and rare gene ontology items on each chromosome, which is helpful to discover functions of cotton chromosomes.</p

Expression of tumour-specific antigens underlies cancer immunoediting

Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1, 2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced2, 3. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy.National Institutes of Health (U.S.) (Grant 1 U54 CA126515-01)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship AwardJohnD. Proctor FoundationDaniel K. Ludwig Schola

Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

<p>Abstract</p> <p>Background</p> <p>Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance <it>in vitro </it>occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7_DOX-2), epirubicin (MCF-7_EPI), paclitaxel (MCF-7_TAX-2), or docetaxel (MCF-7_TXT). During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters.</p> <p>Results</p> <p>In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance.</p> <p>Conclusion</p> <p>This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does occur at the threshold dose, the magnitude of resistance cannot be attributed solely to changes in drug accumulation or the activity of drug transporters. The identities of these additional drug-transporter-independent mechanisms are discussed, including their likely clinical relevance.</p